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1.
J Colloid Interface Sci ; 605: 582-591, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34343731

RESUMO

Diabetes is a metabolic disease that is affecting an ever-increasing number of people worldwide, resulting in increased burdens on healthcare systems and societies. Constant monitoring of blood glucose levels is required to prevent serious or even deadly complications. One major challenge of diabetes management is the simple and timely administration of insulin to facilitate consistent blood glucose regulation and reduce the incidence of hypoglycemia. With this research, we construct an insulin delivery system, the delivery system is comprised of phenylboronic acid based fluorescent probes, which is used as glucose responsive linkers, mesoporous silica nanoparticles providing an insulin reservoir, and zinc oxide nanoparticles used as gate keepers. The system with glucose sensitive responsive linker exhibits controlled release of insulin under high glucose concentrations, providing prolonged blood glucose regulation and no risks of hypoglycemia. Furthermore, the system is combined with a hyaluronic-acid based microneedle patch, which exhibit efficient skin penetration for transdermal delivery. With our system, the nanoparticles provide outstanding in vivo glucose regulation when administrated by subcutaneous injection or via transdermal microneedle patch. We anticipate that our biocompatible smart glucose responsive microneedle patch (SGRM patch) will facilitate the development of clinically useful systems.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hipoglicemia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Hipoglicemia/tratamento farmacológico , Insulina , Agulhas
2.
Food Chem ; 371: 131106, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34543925

RESUMO

Type 2 diabetes (T2D) is a metabolic disease characterized by hyperglycemia. Intake of dietary fiber is inversely associated with risks of T2D. Here, metabolomics and 16S rRNA gene sequencing were employed to investigate the effects of arabinoxylan on gut microbiota and their metabolites in type 2 diabetic rats. T2D increased the abundance of opportunistic pathogens (such as Desulfovibrio and Klebsiella) and the levels of 12α-hydroxylated bile acids and acylcarnitines (C3) in diabetic rats, which eventually contribute to insulin resistance and hyperglycemia. Supplementation with arabinoxylan promoted the growth of fiber-degrading bacteria to increase short-chain fatty acids (SCFAs), as well as decreased the abundance of opportunistic pathogens. Arabinoxylan treatment also decreased the concentrations of 12α-hydroxylated bile acids, and increased the levels of equol, indolepropionate, and eicosadienoic acid. This study indicated that the beneficial effects of arabinoxylan on T2D may be partially attributed to the modification of gut microbiota and related metabolites.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , RNA Ribossômico 16S , Ratos , Xilanos
3.
Braz J Med Biol Res ; 54(12): e11550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730682

RESUMO

Following radiotherapy, patients have decreased bone mass and increased risk of fragility fractures. Diabetes mellitus (DM) is also reported to have detrimental effects on bone architecture and quality. However, no clinical or experimental study has systematically characterized the bone phenotype of the diabetic patients following radiotherapy. After one month of streptozotocin injection, three-month-old male rats were subjected to focal radiotherapy (8 Gy, twice, at days 1 and 3), and then bone mass, microarchitecture, and turnover as well as bone cell activities were evaluated at 2 months post-irradiation. Micro-computed tomography results demonstrated that DM rats exhibited greater deterioration in trabecular bone mass and microarchitecture following irradiation compared with the damage to bone structure induced by DM or radiotherapy. The serum biochemical, bone histomorphometric, and gene expression assays revealed that DM combined with radiotherapy showed lower bone formation rate, osteoblast number on bone surface, and expression of osteoblast-related markers (ALP, Runx2, Osx, and Col-1) compared with DM or irradiation alone. DM plus irradiation also caused higher bone resorption rate, osteoclast number on bone surface, and expression of osteoclast-specific markers (TRAP, cathepsin K, and calcitonin receptor) than DM or irradiation treatment alone. Moreover, lower osteocyte survival and higher expression of Sost and DKK1 genes (two negative modulators of Wnt signaling) were observed in rats with combined DM and radiotherapy. Together, these findings revealed a higher deterioration of the diabetic skeleton following radiotherapy, and emphasized the clinical importance of health maintenance.


Assuntos
Diabetes Mellitus Experimental , Animais , Osso e Ossos , Humanos , Masculino , Osteogênese , Ratos , Estreptozocina , Microtomografia por Raio-X
4.
Nanoscale ; 13(44): 18632-18646, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34734624

RESUMO

We report a one-pot facile synthesis of highly photoresponsive bovine serum albumin (BSA) templated bismuth-copper sulfide nanocomposites (BSA-BiZ/CuxS NCs, where BiZ represents in situ formed Bi2S3 and bismuth oxysulfides (BOS)). As-formed surface vacancies and BiZ/CuxS heterojunctions impart superior catalytic, photodynamic and photothermal properties. Upon near-infrared (NIR) irradiation, the BSA-BiZ/CuxS NCs exhibit broad-spectrum antibacterial activity, not only against standard multidrug-resistant (MDR) bacterial strains but also against clinically isolated MDR bacteria and their associated biofilms. The minimum inhibitory concentration of BSA-BiZ/CuxS NCs is 14-fold lower than that of BSA-CuxS NCs because their multiple heterojunctions and vacancies facilitated an amplified phototherapeutic response. As-prepared BSA-BiZ/CuxS NCs exhibited substantial biofilm inhibition (90%) and eradication (>75%) efficiency under NIR irradiation. Furthermore, MRSA-infected diabetic mice were immensely treated with BSA-BiZ/CuxS NCs coupled with NIR irradiation by destroying the mature biofilm on the wound site, which accelerated the wound healing process via collagen synthesis and epithelialization. We demonstrate that BSA-BiZ/CuxS NCs with superior antimicrobial activity and high biocompatibility hold great potential as an effective photosensitive agent for the treatment of biofilm-associated infections.


Assuntos
Diabetes Mellitus Experimental , Animais , Antibacterianos/farmacologia , Biofilmes , Catálise , Camundongos , Testes de Sensibilidade Microbiana
5.
Zhonghua Shao Shang Za Zhi ; 37(11): 1024-1035, 2021 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-34794254

RESUMO

Objective: To study the effects of reactive oxygen species (ROS)-responsive antibacterial microneedles (MNs) on the full-thickness skin defect wounds with bacterial colonization in diabetic mice. Methods: Experimental research methods were adopted. The ROS-responsive crosslinker N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1, N1, N3, N3-tetramethylpropane-1,3-diaminium (TSPBA) was first synthesized, and then the polyvinyl alcohol (PVA)-TSPBA MNs, PVA-ε-polylysine (ε-PL)-TSPBA MNs, PVA-TSPBA-sodium hyaluronate (SH) MNs, and PVA-ε-PL-TSPBA-SH MNs were prepared by mixing corresponding ingredients, respectively. The PVA-TSPBA MNs were placed in pure phosphate buffer solution (PBS) and PBS containing hydrogen peroxide, respectively. The degradation of MNs immersed for 0 (immediately), 3, 7, and 10 days was observed to indicate their ROS responsiveness. The standard strains of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) cultured in Luria-Bertani medium containing hydrogen peroxide were divided according to the random number table (the same grouping method below) into blank control group (without any treatment, the same below) and 0 g/L ε-PL group, 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group with which PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL were co-cultured, respectively. Bacterial growth was observed after 24 h of culture, and the relative survival rate of bacteria was calculated (n=3). The mouse fibroblast cell line 3T3 cells at logarithmic growth stage (the same growth stage below) were divided into blank control group and 0 g/L ε-PL group, 1.0 g /L ε-PL group, 5.0 g /L ε-PL group, and 10.0 g /L ε-PL group in which cells were cultured in medium with the extract from PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL, respectively. Cell growth was observed after 24 h of culture by optical microscopy, and the relative survival rate of cells was detected and calculated by cell counting kit 8 (CCK-8) assay to indicate the cytotoxicity (n=6). Both PVA-TSPBA MNs and PVA-TSPBA-SH MNs were taken, the morphology of the two kinds of MNs was observed by optical microscopy, and the mechanical properties of the two kinds of MNs were tested by microcomputer controlled electronic universal testing machine (denoted as critical force, n=6). Six male BALB/c mice aged 6-8 weeks (the same gender and age below) were divided into PVA-TSPBA group and PVA-TSPBA-SH group, with 3 mice in each group. After pressing the skin on the back of mice vertically with the corresponding MNs for 1 minute, the skin condition was observed at 0, 10, and 20 min after pressing. Another batch of 3T3 cells were divided into blank control group, 0 g/L ε-PL group and simple 5.0 g/L ε-PL group which were cultured with the extract of PVA-ε-PL-TSPBA MNs containing the corresponding concentration of ε-PL, and 5.0 g/L ε-PL+SH group which were cultured with the extract of PVA-ε-PL-TSPBA-SH MNs with 5.0 g/L ε-PL. The CCK-8 assay was performed to detect and calculate the relative survival rate of cells cultured for 24, 48, and 72 h to indicate the cell proliferation activity (n=6). Eighteen BALB/c mice were induced into diabetic mice model by high-sugar and high-fat diet combined with streptozotocin injection and then divided into sterile dressing group, 0 g/L ε-PL+SH group, and 5.0 g/L ε-PL+SH group, with 6 mice in each group. A full-thickness skin defect wound was made on the back of each mouse, and S. aureus solution was added to make a full-thickness skin defect wound with bacterial colonization model for diabetic mouse. The wounds of mice in 0 g/L ε-PL+SH group and 5.0 g/L ε-PL+SH group were covered with PVA-ε-PL-TSPBA-SH MNs with the corresponding concentration of ε-PL, and the wounds of mice in the 3 groups were all covered with sterile surgical dressings. The wound healing was observed on post injury day (PID) 0, 3, 7, and 12, and the wound healing rate on PID 3, 7, and 12 was calculated. On PID 12, the skin tissue of the wound and the wound margin were stained with hematoxylin and eosin to observe the growth of new epithelium and the infiltration of inflammatory cells. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, Mann-Whitney U test, and Bonferroni test. Results: With the extension of the immersion time, the PVA-TSPBA MNs in PBS containing hydrogen peroxide gradually dissolved and completely degraded after 10 days of immersion. The PVA-TSPBA MNs in pure PBS only swelled but did not dissolve. After 24 h of culture, there was no growth of S. aureus in 5.0 g/L ε-PL group or 10.0 g/L ε-PL group, and there was no growth of E. coli in 10.0 g/L ε-PL group. The relative survival rate of S. aureus was significantly lower in 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group than in blank control group (P<0.05 or P<0.01). The relative survival rate of E. coli was significantly lower in 5.0 g/L ε-PL group and 10.0 g/L ε-PL group than in blank control group (P<0.01). After 24 h of culture, the cells in blank control group, 0 g/L ε-PL group, 1.0 g/L ε-PL group, 5.0 g/L ε-PL group, and 10.0 g/L ε-PL group all grew well, and the relative survival rate of cells was similar among the groups (P>0.05). The needle bodies of PVA-TSPBA MNs and PVA-TSPBA-SH MNs were both quadrangular pyramid-shaped and neatly arranged, and the needle bodies of PVA-TSPBA-SH MNs was more three-dimensional and more angular. The critical force of PVA-TSPBA-SH MNs was significantly higher than that of PVA-TSPBA MNs (Z=3.317, P<0.01). The MNs in PVA-TSPBA+SH group penetrated the skin of mice at 0 min after pressing, and the pinholes partially disappeared after 10 min and completely disappeared after 20 min, while the MNs in PVA-TSPBA group failed to penetrate the skin of mice. After 24, 48, and 72 h of culture, the proliferation activity of the cells in 5.0 g/L ε-PL+SH group was significantly higher than that of blank control group (P<0.05 or P<0.01). In sterile dressing group, the wounds of mice healed slowly and exuded more. The wound healing speed of mice in 0 g/L ε-PL+SH group was similar to that of sterile dressing group in the early stage but was faster than that of sterile dressing group in the later stage, with moderate exudation. The wound healing of mice in 5.0 g/L ε-PL+SH group was faster than that in the other two groups, with less exudation. The wound healing rates of mice in 5.0 g/L ε-PL+SH group were (40.6±4.2)%, (64.3±4.1)%, and (95.8±2.4)% on PID 3, 7, and 12, which were significantly higher than (20.4±2.7)%, (38.9±2.2)%, and (59.1±6.2)% in sterile dressing group and (21.6±2.6)%, (44.0±1.7)%, and (82.2±5.3)% in 0 g/L ε-PL+SH group (P<0.01). The wound healing rates of mice in 0 g/L ε-PL+SH group on PID 7 and 12 were significantly higher than those in sterile dressing group (P<0.05 or P<0.01). On PID 12, the wounds of mice in 5.0 g/L ε-PL+SH group were almost completely epithelialized with less inflammatory cell infiltration, the wounds of mice in 0 g/L ε-PL+SH group were partially epithelialized with a large number of inflammatory cell infiltration, and no obvious epithelialization but a large number of inflammatory cell infiltration was found in the wounds of mice in sterile dressing group. Conclusions: The composite MNs prepared by TSPBA, PVA, ε-PL, and SH can successfully penetrate mouse skin and slowly respond to ROS in the wound to resolve and release antibacterial substances, inhibit bacterial colonization, and promote the repair of full-thickness skin defect wounds with bacterial colonization in diabetic mice.


Assuntos
Diabetes Mellitus Experimental , Animais , Antibacterianos/farmacologia , Escherichia coli , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio , Staphylococcus aureus
6.
Molecules ; 26(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34771066

RESUMO

Panax ginseng was employed in the treatment of "Xiao-Ke" symptom, which nowadays known as diabetes mellitus, in traditional Chinese medicine for more than a thousand years. Ginsenoside Re was the major pharmacologic ingredient found abundantly in ginseng. However, the anti-diabetic of Ginsenoside Re and its underlying mechanism in metabolic level are still unclear. Serum and urine metabolomic method was carried out to investigate the anti-diabetic pharmacological effects and the potential mechanism of Ginsenoside Re on high-fat diet combined streptozotocin-induced type 2 diabetes mellitus (T2DM) rats based on ultra-high-performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). Serum and urine samples were collected from the control group (CON), T2DM group, metformin (MET) treatment group, and ginsenoside Re treatment group after intervention. The biochemical parameters of serum were firstly analyzed. The endogenous metabolites in serum and urine were detected by UHPLC-MS. The potential metabolites were screened by multivariate statistical analysis and identified by accurate mass measurement, MS/MS, and metabolite databases. The anti-diabetic-related metabolites were analyzed by KEGG metabolic pathway, and its potential mechanism was discussed. The treatment of ginsenoside Re significantly reduced the blood glucose and serum lipid level improved the oxidative stress caused by T2DM. Biochemical parameters (urea nitrogen, uric acid) showed that ginsenoside Re could improve renal function in T2DM rats. Respective 2 and 6 differential metabolites were found and identified in serum and urine of ginsenoside Re compared with T2DM group and enriched in KEGG pathway. Metabolic pathways analysis indicated that the differential metabolites related to T2DM were mainly involved in arachidonic acid metabolism, Vitamin B6, steroid hormone biosynthesis, and bile secretion metabolic pathways. This study verified the anti-diabetic and anti-oxidation effects of ginsenoside Re, elaborated that ginsenoside Re has a good regulation of the metabolic disorder in T2DM rats, which could promote insulin secretion, stimulated cannabinoid type 1 receptor (CB1), and CaMKK ß to activate AMPK signaling pathway, inhibited insulin resistance, and improved blood glucose uptake and diabetic nephropathy, so as to play the role of anti-diabetic.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ginsenosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metabolômica , Animais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Ginsenosídeos/análise , Ginsenosídeos/metabolismo , Hipoglicemiantes/análise , Hipoglicemiantes/metabolismo , Masculino , Espectrometria de Massas , Panax/química , Ratos , Ratos Wistar , Estreptozocina
7.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 534-537, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816668

RESUMO

Objective: To investigate the effects of Sitagliptin on myocardial remodeling and autophagy in diabetic mice and its possible mechanisms. Methods: C57 mice aged ten weeks were treated with streptozocin (STZ) at the dose of 50 mg/(kg·d) by intraperitoneal injections for five consecutive days, and the level of fasting blood glucose concentration was higher than 16.7 mmol/l after seven days indicated that the diabetic model was established successfully. Mice were divided into four groups, including control group (n=10) which was intraperitoneally injected with the same volum of saline, the model group (n=8), Sitagliptin treatment group(diabetic mice were treated with Sitagliptin at the dose of 10 mg/(kg·d)by gavage, n=8) and the inhibitor group(diabetic mice were treated with Compound C, an AMPK inhibitor, at the dose of 10 mg/(kg·d) by intraperitoneal injection, n=8). After six weeks, all the mices were weighted and then put to death and the hearts were separated to caculate ventricular /body weight ratio. Hemaloxylin-Eosin (HE) staining was used to observe the cell morphology and masson staining was used to observe interstitial fibrosis. Western blot was used to test the heart protein expressions of Connexin43(Cx43), adenosine 5'-monophosphate -activated protein kinase (AMPK), brain natriuretic peptide(BNP), transforming growth factor(TGF-ß) and LC3B. Results: After six weeks of treatment, compared with control group, the ventricular /body weight ratio was improved (P<0.05), The cardiomyocyte hypertrophy and increased fibrosis were observed in the model group. The expression levels of BNP and TGF-ß were increased, while the expression levels of Cx43,LC3B and AMPK were decreased significantly(P<0.05). However, compared with model group, treatment with Sitagliptin decreased BNP, TGF-ß protein levels and increased Cx43 and LC3B protein levels, while Compound C could inhibit the upregulation of Cx43, LC3B and AMPK protein (P<0.05). Conclusion: Sitagliptin could improve cardiac hypertrophy and decrease interstitial fibrosis and AMPK-related signaling pathways was involved in the regulation of Cx43 and autophagy.


Assuntos
Diabetes Mellitus Experimental , Fosfato de Sitagliptina , Animais , Autofagia , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Miocárdio , Fosfato de Sitagliptina/farmacologia , Estreptozocina
8.
Acta Cir Bras ; 36(9): e360907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755767

RESUMO

PURPOSE: To assess the effects of adipocyte-derived stem cell (ASC)-injection on the survival of surgical flaps under ischemia in diabetic rats. METHODS: Diabetes was induced in 30 male Wistar rats using streptozotocin (55 mg/kg). After eight weeks, epigastric flap (EF) surgery was performed. The animals were divided into control (CG), medium-solution (MG), and ASC groups. The outcomes were: the survival area (SA), the survival/total area rate (S/TR), and expression levels (EL) of genes: C5ar1, Icam1, Nos2, Vegf-a. RESULTS: In the ASC group, compared to CG, we observed improved flap SA (CG-420 mm2 vs. ASC-720 mm2; p=0.003) was observed. The S/TR analysis was larger in the ASC group (78%) than the CG (45%). This study showed an increase in the Vegf-a EL in the ASC group (2.3) vs. CG (0.93, p=0.0008). The Nos2 EL increased four-fold in the ASC group compared to CG, and C5ar1 EL decreased almost two-fold in the ASC group vs. the CG (p=0.02). There was no difference among the groups regarding Icam1 EL. Compared to the MG, the ASC group had a bigger flap SA (720 mm2 vs. 301 mm2, respectively), a bigger S/TR (78% vs. 32%, p=0.06, respectively) and increased EL of Vegf-a (2.3 vs. 1.3, respectively). No difference between ASC-group and MG was seen regarding Nos2 (p=0.08) and C5ar1 (p=0.05). CONCLUSIONS: This study suggests that ASCs increase the survival of EF under IR in diabetic rats.


Assuntos
Diabetes Mellitus Experimental , Adipócitos , Tecido Adiposo , Animais , Isquemia , Masculino , Ratos , Ratos Wistar , Células-Tronco , Retalhos Cirúrgicos
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(10): 1519-1526, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34755667

RESUMO

OBJECTIVE: To explore the role of cell cycle checkpoint kinase 1/2 (CHK1/2) in mediating the inhibitory effect of oxymatrine (OMT) against renal inflammation and fibrosis in diabetic rats. METHODS: SD rats were randomly divided into normal control group, diabetes model group (DM) and OMT treatment group (n=6). HE and Masson staining were used to observe histopathological changes of the renal tissue, and the expressions of CHK1, CHK2, p-CHK1 and p-CHK2 were localized by immunohistochemical staining. The contents of interleukin-6 (IL-6) and IL-1ß in the renal tissue were detected using ELISA, and the expression levels of CHK1, CHK2, p-CHK1, p-CHK2, type Ⅲ collagen (Col-Ⅲ), type Ⅳ collagen (Col-Ⅳ), and fibronectin (FN) were determined using Western blotting. The changes in the expressions of CHK1, CHK2, p-CHK1, p-CHK2, Col-Ⅲ, Col-Ⅳ and FN proteins were also examined with Western blotting in NRK-52E cells in response to high glucose exposure, OMT treatment and siRNA-mediated CHK1/2 knockdown. RESULTS: In diabetic rats, OMT treatment significantly decreased the levels of blood glucose, serum creatinine and 24 h urinary protein (P < 0.05) and obviously improved inflammatory cell infiltration and fibrosis phenotype in the renal tissue (P < 0.05). CHK1 and CHK2 were mainly expressed in the cytoplasm and nuclei of renal tubule cells, and their phosphorylation levels were significantly higher in DM group than in the control group and OMT group. OMT treatment significantly decreased the protein expression levels of p-CHK1, p-CHK2, Col-Ⅲ, Col-Ⅳ and FN in the renal tissue of diabetic rats and in NRK-52E cells exposed to high glucose (P < 0.05). In NRK-52E cells, CHK1/2 knockdown resulted in significant reduction of the protein expressions of p-CHK1/2, Col-Ⅲ, Col-Ⅳ and FN (P < 0.05). CONCLUSION: The inhibitory effects of OMT against renal inflammation and fibrosis in diabetic rats are mediated probably by lowered phosphorylation levels of CHK1 and CHK2, which result in reduced release of the downstream inflammatory mediators and decreased secretion and deposition of extracellular matrix.


Assuntos
Diabetes Mellitus Experimental , Alcaloides , Animais , Diabetes Mellitus Experimental/complicações , Fibrose , Inflamação/tratamento farmacológico , Fosforilação , Quinolizinas , Ratos , Ratos Sprague-Dawley
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 638-643, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821098

RESUMO

Objective: To investigate the effects of Moringa leaves on the cognitive dysfunction and apoptosis of hippocampal neurons in diabetic rats induced by streptozotocin (STZ). Methods: Fifty male SD rats were selected, and 10 rats were randomly selected as the control group. The other 40 rats were treated with STZ at the dose of 25 mg/kg by intraperitoneal injection. The 40 diabetic rats were randomly divided into model group, Moringa oleifera low-dose, medium-dose and high-dose group. The rats in Moringa oleifera groups were treated with Moringa oleifera at the doses of 2.0, 4.0 and 8.0 g/kg by gavage, the control group and model group were treated with the same amount of normal saline once a day, for 8 weeks. Morris water maze test was used to evaluate the learning and memory ability of rats. Pathological changes of hippocampal neurons and expressions of Bax, caspase-3 and bcl-2 protein in each group were observed by the sections were stained with HE staining and immunohistochemistry. Enzyme linked immunosorbent assay (ELISA) was used to detect tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rat. Results: compared with the control group, the blood glucose of the model group was increased significantly (P<0.01), and the blood insulin level was decreased significantly (P<0.05); compared with the model group, the blood glucose values of Moringa oleifera groups were decreased significantly (P<0.05, P<0.01), and the blood insulin levels of middle and high dose Moringa oleifera group were increased significantly (P<0.05, P<0.01). There was no significant difference in FBG and INS among the three groups (P>0.05). In Morris water maze test, compared with the model group, the latency of Moringa oleifera groups was significantly shorter (P<0.05); the residence time in target quadrant of Moringa oleifera groups with different doses was significantly prolonged (P<0.05). Compared with the model group, the contents of TNF - α, IL-6 and protein expression in low, medium and high dose groups of Moringa oleifera were decreased significantly (P<0.05). HE staining and immunohistochemical staining results showed that Moringa oleifera medium dose group was positive, brown yellow, fine granular, compared with the model group. The number of neuronal apoptosis was significantly reduced in the middle dose group (53.21±7.19,P<0.01); the protein expressions of Bax, caspase-3 and the ratio of Bax/Bcl-2 in hippocampus were significantly decreased in the middle dose group (P<0.05). Conclusion: The mechanisms of Moringa leaves on the cognitive dysfunction and apoptosis of hippocampal neurons may be related to regulating the protein expressions of Bax, Bcl-2 and Caspase-3, reducing the contents of inflammatory factors TNF-α and IL-6.


Assuntos
Diabetes Mellitus Experimental , Animais , Apoptose , Cognição , Diabetes Mellitus Experimental/tratamento farmacológico , Hipocampo , Neurônios , Folhas de Planta , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 665-672, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821103

RESUMO

Objective: To investigate the effects of aerobic exercise plus spirulina polysaccharide(SP) supplement on the related protein expressions of p75NTR signal in hippocampal and the improvement of learning and memory of type 2 diabetes rats. Methods: The model of type 2 diabetic rats was established by fed high-fat diet for four weeks together with intraperitoneal injecting a low dose of STZ. The model rats were randomly divided into diabetic model group(B),diabetic exercise group(C),diabetic+SP group(D)and diabetic exercise+SP group(E), another normal control group(A)without any intervention was set up,12 rats in each group. The rats in Group C and E were treated with intervention of swimming training for six weeks. The rats in Group D and E were treated with SP intragastrically for 6 weeks. Learning and memory abilities were observed by Morris water maze test. The hippocampus cell apoptosis was observed by Tunnel staining, and BDNF content and the expressions of p75NTR, cleaved caspase-3 of hippocampus were tested by ELISA, Western blot and immunohistochemistry, respectively. At the same time, the changes of blood glucose and levels of serum insulin were examined. Results: ①Compared with Group A at different time points, the body weight of Group B was decreased significantly(P<0.01). Compared with Group B at different time points, the body weight of Group C,D and E had no difference (P>0.05). Compared with Group A, levels of the blood glucose and serum insulin Group B were increased significantly(P<0.01).Compared with Group B, the levels in the intervention groups were decreased significantly (P<0.01); ②Compared with Group A, the escape latencies of Group B were prolonged significantly(P<0.01), platform quadrant residence duration and the times of crossing platform were decreased (P<0.01). Compared with Group B, the escape latencies of the intervention groups were shortened (P<0.05 or P<0.01), and the times of crossing platform were increased (P<0.05 or P<0.01). ③Compared with Group B, the neural cells apoptosis of the intervention rats was decreased, and the protein expressions of p75NTR and cleaved caspase-3 were decreased (P<0.05 or P<0.01), however the expression of BDNF was increased significantly (P<0.05 or P<0.01). Conclusion: Aerobic exercise and SP supplement can improve the learning-memory ability of type 2 diabetes rats, and the improvement effect of exercise combined with SP is markedly better than that of exercise and SP alone, the mechanism might be related to better regulating p75NTR signal related protein expressions and then inhibiting apoptosis in hippocampus of rats with type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Spirulina , Animais , Diabetes Mellitus Experimental/terapia , Hipocampo , Polissacarídeos , Ratos , Ratos Sprague-Dawley , Natação
12.
Front Cell Infect Microbiol ; 11: 714440, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595130

RESUMO

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Diabetes Mellitus Tipo 1/complicações , Humanos , Influenza Humana/complicações , Camundongos , Infecções por Orthomyxoviridae/complicações
13.
Medicina (Kaunas) ; 57(10)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34684108

RESUMO

Background and Objectives: Enamel matrix derivative (EMD) is a biomaterial used for periodontal regenerative therapy due to its properties of stimulating cementum development and bone synthesis. Diabetes is a chronic condition that affects healing and predisposes to infection. The aim of this review was to evaluate the current studies available on the application and results of EMD for periodontal regenerative therapy under diabetic conditions. Materials and Methods: Five databases (PubMed, ResearchGate, Scopus, Web of Science and Google Scholar) were searched for relevant articles, using specific keywords in different combinations. The inclusion criteria were clinical trials, case reports, case studies, and animal studies published in English, where periodontal treatment for bone defects includes EMD, and it is performed under diabetic conditions. Results: Of the 310 articles resulted in search, five studies published between 2012 and 2020 met the inclusion criteria and were selected for the current review. In human studies, the use of EMD in infrabony defects showed favorable results at follow-up. In animal studies, periodontal regeneration was reduced in diabetic rats. Conclusions: EMD might promote bone healing when used under diabetic conditions for the regenerative periodontal therapy. Due to limited number of studies, more data are required to sustain the effects of EMD therapy in diabetic settings.


Assuntos
Perda do Osso Alveolar , Proteínas do Esmalte Dentário , Diabetes Mellitus Experimental , Animais , Osteogênese , Ratos , Cicatrização
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(9): 1342-1349, 2021 Aug 31.
Artigo em Chinês | MEDLINE | ID: mdl-34658348

RESUMO

OBJECTIVE: To investigate the effect of 1-deoxynojirimycin (DNJ) for improving diabetic liver fibrosis and explore the underlying mechanism. METHODS: Mouse models of type 2 diabetes were established in 10 Kunming mice by high-fat diet feeding for 8 weeks and intraperitoneal injection of STZ, with 5 mice receiving intraperitoneal injection of citrate buffer solution with normal feeding as the control group. The mouse models were randomized into two groups (n=5) for further highfat feeding (model group) and additional treatment with 10% DNJ in drinking water (200 mg · kg-1 per day; DNJ group) for 8 weeks. The mice were monitored for changes in body weight (BW), blood glucose, serum total cholesterol (TC), triglyceride (TG) and superoxide dismutase (SOD) levels. The pathological changes in the liver tissue were observed using HE and Sirius Red staining, and the solubility of collagens in the liver tissues was determined. The expression levels of MCP-1, TNF-α, IL-1ß and TGF-ß1 mRNA were detected with real-time PCR, and the protein expressions of α-SMA and collagen2 (ColA2) were determined with Western blotting. In the in vitro experiment, mouse fibroblasts L929 cells were pretreated with DNJ (10 µg/ mL) or PBS for 30 min followed by culture in high-glucose medium for 24 h, and the level of ROS production was measured using dihydroethidium (DHE) staining. RESULTS: In the mouse model of type 2 diabetes, DNJ treatment significantly lowered serum level of glucose, TC, and TG (P < 0.05) and increased serum SOD activity (P < 0.05). DNJ obviously attenuated liver fibrosis in the diabetic mice, as shown by alleviated cross-linking of collagens and reduced contents of pepsin-solubilized collagen (PSC) and total collagen (P < 0.05). DNJ treatment also significantly reduced the overexpression of the proinflammatory cytokines and fibrosis-related cytokines induced by diabetes (P < 0.05). In L929 cells exposed to high glucose, pretreatment with DNJ significantly lowered the intensity of red fluorescence in DHE staining. CONCLUSION: DNJ can attenuate type 2 diabetes-induced liver fibrosis in mice through its hypoglycemic, anti-inflammatory and anti-oxidative effects.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , 1-Desoxinojirimicina/uso terapêutico , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cirrose Hepática , Camundongos , Camundongos Endogâmicos C57BL
15.
Zhonghua Shao Shang Za Zhi ; 37(9): 860-868, 2021 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-34645152

RESUMO

Objective: To investigate the effects and mechanism of hepatocyte growth factor (HGF)-modified human adipose mesenchymal stem cells (ADSCs) on the wound healing of full-thickness skin defects in diabetic rats. Methods: The experimental research method was adopted. The discarded abdominal adipose tissue was collected from a 35-year-old healthy female who underwent abdominal liposuction in the Department of Plastic Surgery of the First Affiliated Hospital of Air Force Medical University in December 2019. The long spindle-shaped primary ADSCs were obtained by collagenase digestion, and the third passage of cells were identified by flow cytometry to positively express ADSCs surface markers CD29 and CD90 and negatively express CD34 and CD45. The third passage of ADSCs were used for the subsequent experiments. ADSCs were transfected with lentivirus-mediated HGF for 4 h (obtaining HGF modified ADSCs) and then routinely cultured for 24 h. The cell morphology was observed under an inverted phase contrast microscope, and the transfection rate was calculated. Eighty-one male Sprague-Dawley rats aged 4 weeks were induced into diabetic rat model by high glucose and high fat diet combined with streptozotocin injection. A full-thickness skin defect wound of 1.5 cm×1.5 cm was made on the back of each rat. The injured rats were divided into phosphate buffer solution (PBS) group, ADSCs alone group, and HGF-modified ADSCs group according to the random number table, with 27 rats in each group. The rats were injected with the same volume of corresponding substances around the wound on post injury day (PID) 1, 3, and 7, respectively. Nine rats in each group were selected according to the random number table, the wound area of whom was measured on PID 0 (immediately), 3, 7, 10, and 14 (after injection on injection day), and the wound healing rates on PID 3, 7, 10, and 14 were calculated. Nine remaining rats in each group were sacrificed after injection on PID 3 and 7, respectively, and the skin tissue around the wound were collected. The mRNA expressions of inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-10 on PID 3 and collagen type Ⅰ and Ⅲ on PID 7 were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction. The expression level of vascular endothelial growth factor (VEGF) was detected by enzyme-linked immunosorbent assay on PID 7. The protein expression of nuclear factor κb-p65 on PID 3 and phosphorylation level of protein kinase B (Akt) on PID 7 were detected by Western blotting. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, least significant difference t test, and Bonferroni correction. Results: After 24 h of culture, the HGF-transfected human ADSCs showed good morphology, which was not different with the non-transfected ADSCs, and the transfection rate reached 90%. On PID 3, 7, 10, and 14, the wound healing rates of rats in HGF-modified ADSCs group were (31.5±1.0)%, (75.2±2.0)%, (92.2±1.3)%, and (99.1±1.8)%, respectively, being significantly higher than (21.4±1.3)%, (61.4±1.5)%, (80.1±2.1)%, and (92.4±1.8)% in PBS group and (25.1±2.1)%, (67.2±1.3)%, (89.3±1.4)%, and (95.1±2.1)% in ADSCs alone group (t=1.452, 0.393, 0.436, 0.211, 4.982, 3.011, 4.211, 7.503, P<0.05 or P<0.01). On PID 3, compared with those in PBS group and ADSCs alone group, the mRNA expressions of TNF-α and IL-1ß and protein expression of nuclear factor κb-p65 in the skin tissue around the wound of rats in HGF-modified ADSCs group were significantly decreased (t=7.281, 17.700, 9.447, 6.231, 13.083, 7.783, P<0.01), and the mRNA expression of IL-10 in the skin tissue around the wound of rats in HGF-modified ADSCs group was significantly increased (t=-6.644, -6.381, P<0.01). On PID 7, compared with those in PBS group and ADSCs alone group, the mRNA expressions of collagen type Ⅰ and Ⅲ, the expression level of VEGF, and the phosphorylation level of Akt in the skin tissue around the wound of rats in HGF-modified ADSCs group were significantly increased (t=-5.126, -4.347, -5.058, -3.367, -10.694, -19.876, -4.890, -6.819, P<0.05 or P<0.01). Conclusions: HGF-modified human ADSCs can significantly promote the wound healing of full-thickness skin defects in diabetic rats. The mechanism may be related to the inhibition of TNF-α and IL-1ß expression, the promotion of IL-10, collagen type Ⅰ and Ⅲ, and VEGF expression, which could be related to the inhibition of nuclear factor κB signaling pathway, and the promotion of Akt signaling pathway.


Assuntos
Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Animais , Feminino , Fator de Crescimento de Hepatócito/genética , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular , Cicatrização
16.
ACS Biomater Sci Eng ; 7(11): 5230-5241, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34699182

RESUMO

Skin regeneration in chronic wounds is often delayed due to persistent inflammation induced by underlying conditions such as diabetes. This effect is mediated, in part, by macrophages present in the wound, which can be stimulated to adopt either pro- or anti-inflammatory phenotypes depending on the status of the local microenvironment. In this work, the prohealing chemokine stromal cell-derived factor-1 alpha (SDF-1α) is controllably released from a hydrogel-based biomaterial to promote skin tissue regeneration and wound closure. This innovative nanocomposite hydrogel system releases liposomal stromal cell-derived factor-1 alpha (lipoSDF) as a new treatment approach for dorsal full-thickness skin wounds in wild-type and diabetic mice. Using this strategy, the recruitment and polarization of macrophages primarily of the anti-inflammatory phenotype were observed, along with a decreased amount of open wound surface area in diabetic mice after 28 days. This was accompanied by histological observations of increased epidermal stratification and dermal angiogenesis. These findings represent an important step of investigation distinctive in its field for developing immunomodulatory biomaterials that are able to influence macrophage phenotype and promote healing as hydrogel-based wound dressings.


Assuntos
Quimiocina CXCL12 , Diabetes Mellitus Experimental , Animais , Macrófagos , Camundongos , Nanogéis , Fenótipo
17.
Rom J Morphol Embryol ; 62(1): 109-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34609413

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease in which immune cells target the pancreatic islets and destroy the ß-cells, resulting in hyperglycemia and decreased plasmatic insulin levels. The non-obese diabetic (NOD) mouse is the most used animal model for studying diabetes because it spontaneously develops T1D and shares similarities with the human disease. A hallmark feature of this model is the appearance of insulitis, defined as an inflammatory cell infiltration of the pancreatic islets. However, a small percentage of NOD mice do not develop overt diabetes even after 28-35 weeks of age. Thus, we questioned the status of the pancreatic islets in these non-diabetic NOD mice, with particular focus on islet inflammation and plasmatic insulin levels, in comparison to pre-diabetic (11 weeks old) and new-onset diabetic mice. Diabetes progression was evaluated by assessing blood glucose and pancreas histology. The inflammatory score was determined on Hematoxylin-Eosin (HE)-stained sections of pancreas. Plasma insulin was detected by enzyme-linked immunosorbent assay (ELISA). The results showed that inflammation increased in an age-dependent manner in all mice, irrespective of their diabetic status. Mostly affected within the analyzed groups were the 28 weeks old non-diabetic NOD mice, in which insulin production was reduced and inversely correlated with the inflammatory status. We conclude that in NOD mice, pancreatic inflammation progresses independently of diabetes onset and clinical signs of disease. Most likely, the NOD females that do not develop overt diabetes preserve a small mass of functional ß-cells, which is able to provide the physiological insulin levels and avoid diabetes onset.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Ilhotas Pancreáticas , Animais , Feminino , Camundongos , Camundongos Endogâmicos NOD , Pâncreas
18.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638608

RESUMO

The delayed healing response of diabetic wounds is a major challenge for treatment. Negative pressure wound therapy (NPWT) has been widely used to treat chronic wounds. However, it usually requires a long treatment time and results in directional growth of wound healing skin tissue. We investigated whether nonthermal microplasma (MP) treatment can promote the healing of skin wounds in diabetic mice. Splint excision wounds were created on diabetic mice, and various wound healing parameters were compared among MP treatment, NPWT, and control groups. Quantitative analysis of the re-epithelialization percentage by detecting Ki67 and DSG1 expression in the extending epidermal tongue (EET) of the wound area and the epidermal proliferation index (EPI) was subsequently performed. Both treatments promoted wound healing by enhancing wound closure kinetics and wound bed blood flow; this was confirmed through histological analysis and optical coherence tomography. Both treatments also increased Ki67 and DSG1 expression in the EET of the wound area and the EPI to enhance re-epithelialization. Increased Smad2/3/4 mRNA expression was observed in the epidermis layer of wounds, particularly after MP treatment. The results suggest that the Smad-dependent transforming growth factor ß signaling contributes to the enhancement of re-epithelialization after MP treatment with an appropriate exposure time. Overall, a short-term MP treatment (applied for 30 s twice a day) demonstrated comparable or better efficacy to conventional NPWT (applied for 4 h once a day) in promoting wound healing in diabetic mice. Thus, MP treatment exhibits promise for treating diabetic wounds clinically.


Assuntos
Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Gases em Plasma/uso terapêutico , Pele/lesões , Cicatrização/fisiologia , Animais , Desmogleína 1/metabolismo , Técnicas In Vitro , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Mutantes , Óxido Nítrico/metabolismo , Regeneração da Pele por Plasma/métodos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reepitelização/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Transdução de Sinais , Pele/patologia , Pele/fisiopatologia , Proteínas Smad/genética , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Cicatrização/genética
19.
Invest Ophthalmol Vis Sci ; 62(13): 7, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34643662

RESUMO

Purpose: Previous studies indicate that leukocytes, notably neutrophils, play a causal role in the capillary degeneration observed in diabetic retinopathy (DR), however, the mechanism by which they cause such degeneration is unknown. Neutrophil elastase (NE) is a protease released by neutrophils which participates in a variety of inflammatory diseases. In the present work, we investigated the potential involvement of NE in the development of early DR. Methods: Experimental diabetes was induced in NE-deficient mice (Elane-/-), in mice treated daily with the NE inhibitor, sivelestat, and in mice overexpressing human alpha-1 antitrypsin (hAAT+). Mice were assessed for diabetes-induced retinal superoxide generation, inflammation, leukostasis, and capillary degeneration. Results: In mice diabetic for 2 months, deletion of NE or selective inhibition of NE inhibited diabetes-induced retinal superoxide levels and inflammation, and inhibited leukocyte-mediated cytotoxicity of retinal endothelial cells. In mice diabetic for 8 months, genetic deletion of NE significantly inhibited diabetes-induced retinal capillary degeneration. Conclusions: These results suggest that a protease released from neutrophils contributes to the development of DR, and that blocking NE activity could be a novel therapy to inhibit DR.


Assuntos
Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/metabolismo , Neutrófilos/enzimologia , Peptídeo Hidrolases/sangue , Retina/metabolismo , Animais , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/etiologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Retina/diagnóstico por imagem
20.
Phytomedicine ; 93: 153741, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34656886

RESUMO

BACKGROUND: Pancreatic inflammation plays a key role in diabetes pathogenesis and progression. Urolithin A (UA), an intestinal flora metabolite of pomegranate, has anti-diabetic, anti-inflammatory and kidney protection effects among others. However, its effects on pancreatic inflammation and the potential mechanisms have not been clearly established. PURPOSE: This study aimed at investigating the molecular mechanisms of UA anti-pancreatic inflammation under a diabetic environment. METHODS: Diabetes induction in male C57BL/6 mice was achieved by a high fat diet and intraperitoneal streptozotocin injections. Then, diabetic mice were orally administered with UA for 8 weeks. In vitro, endoplasmic reticulum stress and MIN6 pancreatic ß cell inflammation were induced using 25 mM glucose and 0.5 mM palmitic acid. The effects of UA were evaluated by immunohistochemistry, Western blot, and enzyme linked immunosorbent assays. Finally, the underlying mechanisms were elucidated using an autophagy inhibitor (chloroquine, CQ) and an AMPK inhibitor (dorsomorphin dihydrochloride). RESULTS: UA significantly inhibited IL-1ß secretion and TXNIP/NLRP3 expression in the pancreas of diabetic mice and in MIN6 pancreatic cells. UA downregulated the ER stress protein, p-PERK, and promoted AMPK phosphorylation. UA activated autophagy to inhibit TXNIP/NLRP3 IL-1ß inflammatory signal, an effect that was reversed by CQ. Dorsomorphin 2HCL, reversed the autophagy-activation and anti-inflammatory effects of UA. Verapamil, clinically applied as an antiarrhythmic drug, is a TXNIP inhibitor for prevention of beta cell loss and diabetes development, but limited by its cardiac toxicity. In this study, verapamil (as positive control) inhibited NLRP3 /IL-1ß signaling in MIN6 cells. Inhibitory effects of UA on TXNIP and IL-1ß were weaker than those of verapamil (both at 50 µM, p < 0.05, p < 0.01). Conversely, inhibitory effects of UA on p62 were stronger, relative to those of verapamil (p < 0.05), and there were no differences in AMPK activation and LC3 enhancement effects between UA and verapamil. CONCLUSION: UA is a potential anti-pancreatic inflammation agent that activates AMPK and autophagy to inhibit endoplasmic reticulum stress associated TXNIP/NLRP3/IL-1ß signal pathway.


Assuntos
Diabetes Mellitus Experimental , Células Secretoras de Insulina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia , Proteínas de Transporte , Cumarínicos , Diabetes Mellitus Experimental/tratamento farmacológico , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Tiorredoxinas/metabolismo
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