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1.
Endocr J ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34629336

RESUMO

Pancreatic neuroendocrine tumors (P-NETs) secreting ectopic adrenocorticotropic hormones (ACTH) are rare and often delayed in diagnosis due to their atypical clinical characteristics. Here, we describe a case of P-NET in the pancreatic tail. The tumor had metastasized to the liver and secreted gastrin and ACTH. A 60-year-old female patient was diagnosed with gastrinoma in the pancreatic tail with liver metastases in 2015. After 3 months, the patient presented refractory hypokalemia and thyroid dysfunction. The final diagnosis was P-NET with ectopic ACTH syndrome (EAS). After cytoreductive surgery and the use of long-acting somatostatin analogs, plasma potassium levels and thyroid function were effectively corrected. Although Sandostatin LAR® Depot and proton pump inhibitors (PPIs) were used throughout the follow-up period, the tumor relapsed 4 years later. After aggressive treatment, including right hepatectomy, microwave coagulation of the left liver, and cholecystectomy, the tumor returned 4 months later. Finally, the patient underwent three hepatic artery embolizations and 12 courses of CAPTEM regimen chemotherapy. The markers of disease were almost maintained in the normal ranges until now. We have followed up on this case for more than 5 years. A timely and comprehensive examination of hormones and immunohistochemistry is essential. The prognosis of P-NET is poor. Regular long-term follow-up and the application of combined therapies are helpful to control the disease and improve the prognosis.

2.
Endocr Connect ; 10(11): 1403-1409, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34636748

RESUMO

A variety of studies have demonstrated the role of lipocalin 2 (LCN2) in both diabetes and neurological disorders. Nevertheless, the relationship between LCN2 and diabetic peripheral neuropathy (DPN) needs to be elucidated in humans. Therefore, this study aimed to investigate the association of LCN2 with DPN in type 2 diabetes (T2D). A total of 207 participants with T2D and 40 participants with normal glucose tolerance (NGT) were included in this study. All participants were classified into DPN group and non-DPN (NDPN) group based on the Toronto Clinical Neuropathy Scoring (TCNS). Demographic and biochemical parameters were measured. Serum LCN2 levels were determined using an ELISA technique. Serum LCN2 levels in NGT group were lower than those in either DPN group (P = 0.000) or NDPN group (P = 0.043), while serum LCN2 levels in DPN group were higher than NDPN group (P = 0.001). Moreover, serum LCN2 levels positively correlated to TCNS scores, which reflects neuropathy severity (r = 0.438, P = 0.000). Multivariate stepwise regression analysis showed that BMI, triglycerides, and diastolic pressure were independently associated with serum LCN2 in DPN. Additionally, logistic regression analysis demonstrated that LCN2 (odds ratio (OR) = 1.009) and diabetes duration (OR = 1.058) were independently associated with the occurrence of DPN in T2D. Our report reveals the association of serum LCN2 with DPN in T2D. LCN2 might be used to evaluate DPN severity and serve a role in the pathogenesis of DPN.

3.
Front Endocrinol (Lausanne) ; 12: 675834, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526965

RESUMO

Background: Berberine (BBR) has therapeutic effect on diabetic nephropathy (DN), but its molecular mechanism is not completely clear. Methods: The DN model was established to observe the therapeutic effect of BBR. The expression levels of lncRNA Gas5 were detected by PCR. The transcriptional regulation of CCAAT enhancer binding protein beta (C/EBPß) on Gas5 was analyzed by chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and luciferase reporter gene assay. The targeted regulation between Gas5 and miR-18a-5p and between miR-18a-5p and C/EBPß 3'-untranslated region (3'-UTR) was also analyzed. Results: In HG environment, BBR decreased the mitochondrial reactive oxygen species (ROS) generation and activated the C/EBPß expression in HK-2 cells; C/EBPß could combine with the reaction element on the promoter of Gas5 to promote its expression. Gas5 also inhibited the miR-18a-5p expression as competing endogenous RNA (ceRNA) and reduce the negative regulatory effect of miR-18a-5p on C/EBPß. BBR could activate C/EBPß/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signal pathway, regulate mitochondrial energy metabolism, and inhibit ROS production and apoptosis by activating C/EBPß/Gas5/miR-18a-5p positive feedback loop in HG environment. It also showed that BBR alleviated streptozotocin (STZ) induced renal injury in DN rats in vivo. Conclusions: This study suggested that BBR could regulate the mitochondrial ROS generation by activating the positive feedback loop of C/EBPß/Gas5/miR-18a-5p.

4.
Front Immunol ; 12: 689337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248978

RESUMO

Cytotoxic T lymphocytes (CTLs) are key players to eliminate tumorigenic or pathogen-infected cells using lytic granules (LG) and Fas ligand (FasL) pathways. Depletion of glucose leads to severely impaired cytotoxic function of CTLs. However, the impact of excessive glucose on CTL functions still remains largely unknown. Here we used primary human CD8+ T cells, which were stimulated by CD3/CD28 beads and cultured in medium either containing high glucose (HG, 25 mM) or normal glucose (NG, 5.6 mM). We found that in HG-CTLs, glucose uptake and glycolysis were enhanced, whereas proliferation remained unaltered. Furthermore, CTLs cultured in HG exhibited an enhanced CTL killing efficiency compared to their counterparts in NG. Unexpectedly, expression of cytotoxic proteins (perforin, granzyme A, granzyme B and FasL), LG release, cytokine/cytotoxic protein release and CTL migration remained unchanged in HG-cultured CTLs. Interestingly, additional extracellular Ca2+ diminished HG-enhanced CTL killing function. Our findings suggest that in an environment with excessive glucose, CTLs could eliminate target cells more efficiently, at least for a certain period of time, in a Ca2+-dependent manner.


Assuntos
Glucose/farmacologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Animais , Células Cultivadas , Glicólise/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Linfócitos T Citotóxicos/metabolismo
5.
Diabetes Res Clin Pract ; 176: 108848, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33945841

RESUMO

AIMS: To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM). METHODS: A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100. RESULTS: Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE): -1.13 (0.05) % and Gla-100: -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference: 0.02%, 95% CI: -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed ≤ 3.9 mmol/L or severe) vs Gla-100 at any time of day or at night (00:00-05:59 h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups. CONCLUSION: Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico/métodos , Insulina Glargina/administração & dosagem , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Relação Dose-Resposta a Droga , Extremo Oriente/etnologia , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/etnologia
7.
Diabetes Care ; 44(6): 1324-1333, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33832957

RESUMO

OBJECTIVE: This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS: After treatment for 24 weeks, the change in HbA1c was -0.93% (95% CI -1.03 to -0.83) (-10.2 mmol/mol [-11.3 to -9.1]) and -0.87% (-0.99 to -0.76) (-9.5 mmol/mol [-10.8 to -8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was -0.05% (95% CI -0.18 to 0.07) (-0.5 mmol/mol [-2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P > 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P < 0.01), but no differences for AEs or SAEs between the two groups were observed (P > 0.05). CONCLUSIONS: SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.


Assuntos
Alcaloides , Diabetes Mellitus Tipo 2 , Morus , Alcaloides/uso terapêutico , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes , Morus/química , Comprimidos , Resultado do Tratamento
8.
World J Diabetes ; 12(4): 466-479, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33889291

RESUMO

BACKGROUND: Atherosclerosis is a major cause of mortality worldwide and is driven by multiple risk factors, including diabetes, which results in an increased atherosclerotic burden, but the precise mechanisms for the occurrence and development of diabetic atherosclerosis have not been fully elucidated. AIM: To summarize the potential role of retinol binding protein 4 (RBP4) in the pathogenesis of diabetic atherosclerosis, particularly in relation to the RBP4-Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. METHODS: Male Wistar rats were randomly divided into three groups, including a control group (NC group), diabetic rat group (DM group), and diabetic atherosclerotic rat group (DA group). The contents of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), fasting insulin (FINS), fasting plasma glucose, and hemoglobin A1c (HbA1c) were measured. Moreover, the adipose and serum levels of RBP4, along with the expression levels of JAK2, phosphorylated JAK2 (p-JAK2), STAT3, phosphorylated STAT3 (p-STAT3), B-cell lymphoma-2 (Bcl-2), and Cyclin D1 in aortic tissues were also measured. Besides, homeostasis model assessment of insulin resistance (HOMA-IR) and atherogenic indexes (AI) were calculated. RESULTS: Compared with the NC and DM groups, the levels LDL-c, TG, TC, FINS, HOMA-IR, RBP4, and AI were upregulated, whereas that of HDL-c was downregulated in the DA group (P < 0.05); the mRNA levels of JAK2, STAT3, Cyclin D1, and Bcl-2 in the DA group were significantly increased compared with the NC group and the DM group; P-JAK2, p-JAK2/JAK2 ratio, p-STAT3, p-STAT3/STAT3 ratio, Cyclin D1, and Bcl-2 at protein levels were significantly upregulated in the DA group compared with the NC group and DM group. In addition, as shown by Pearson analysis, serum RBP4 had a positive correlation with TG, TC, LDL-c, FINS, HbA1C, p-JAK2, p-STAT3, Bcl-2, Cyclin D1, AI, and HOMA-IR but a negative correlation with HDL-c. In addition, multivariable logistic regression analysis showed that serum RBP4, p-JAK2, p-STAT3, and LDL-c were predictors of the presence of diabetic atherosclerosis. CONCLUSION: RBP4 could be involved in the initiation or progression of diabetic atherosclerosis by regulating the JAK2/STAT3 signaling pathway.

9.
Diabetes Obes Metab ; 23(8): 1754-1764, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33769656

RESUMO

AIM: To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. MATERIAL AND METHODS: This multicentre phase 3 trial included a 24-week randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28-week treatment, and patients on henagliflozin during 24-week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24. RESULTS: At Week 24, the least squares mean HbA1c changes versus placebo from baseline were - 0.76% (-8.3 mmol/mol) and - 0.80% (-8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported. CONCLUSIONS: Henagliflozin 5 mg or 10 mg as add-on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Glicemia , Compostos Bicíclicos Heterocíclicos com Pontes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Resultado do Tratamento
10.
Diabetologia ; 64(5): 1066-1078, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33687487

RESUMO

AIMS/HYPOTHESIS: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes. METHODS: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 µg) for 12 weeks. The primary endpoint was the change in HbA1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA1c < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug. RESULTS: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 µg, 150 µg and 200 µg groups). At the end of 12 weeks, mean differences in HbA1c in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 µg, 150 µg and 200 µg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA1c. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death. CONCLUSIONS/INTERPRETATION: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

11.
World J Clin Cases ; 9(8): 1923-1930, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33748243

RESUMO

BACKGROUND: p.Tyr329fs is a cytochrome P450c17 mutation among Chinese individuals. However, data on 17-α-hydroxylase deficiency caused by cytochrome P450c17 p.Tyr329fs homozygous mutation are lacking. This paper is a case report of three patients homozygous for p.Tyr329fs who were diagnosed with 17-α-hydroxylase deficiency between 2005 and 2019. CASE SUMMARY: Case 1 presented with hypertension, hypokalemia, sexual infantilism and delayed bone age. The patient had a 46, XY karyotype, was homozygous for p.Tyr329fs and was recently treated with dexamethasone 0.375 mg qn. Case 2 presented with hypokalemia, sexual infantilism, osteoporosis and delayed bone age. The patient had a 46, XY karyotype, was homozygous for p.Tyr329fs and was treated with dexamethasone 0.75 mg qn at the last follow-up. Serum potassium and blood pressure could be maintained within normal range for cases 1 and 2. Case 3 presented with amenorrhea, sexual infantilism, osteopenia and delayed bone age. The patient had a 46, XX karyotype, was homozygous for p.Tyr329fs and was treated with dexamethasone 0.75 mg qn and progynova 1 mg qd. Outpatient follow-up revealed an adrenocorticotropic hormone (8 AM) of < 5.00 pg/mL. CONCLUSION: The homozygous p.Tyr329fs mutation usually manifests as a combined deficiency, and definitive diagnosis depends primarily on genetic testing.

12.
J Diabetes Res ; 2021: 9526701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33490288

RESUMO

The induction of inflammation and cytokine storm was proposed to play a critical role in COVID-19. This study is aimed at investigating the relationship between glucose metabolism and the inflammatory state of inpatients with COVID-19. 71 inpatients with COVID-19 were classified into nondiabetes mellitus (NDM) group, impaired fasting glucose (IFG) group, and diabetes mellitus (DM) group. The average hospitalization days were significantly shorter in DM patients when compared with patients in the IFG group and NDM group. CD4+ T cell percentage was higher while CD8+ T cells percentage was lower in the DM group than those in the NDM group. The serum levels of IL-6, IL-2, IL-10, and INF-γ in the DM group were upregulated when compared with those in the NDM group. The serum levels of TNF-α, IL-4, IL-2, IL-10, and INF-γ were significantly higher in the DM group than those in the IFG group. A significant difference was observed in CD4+ T cell, CD4+/CD8+ ratio percentage, IL-6, and IL-10 between the NDM group and DM group with adjusted BMI. In conclusion, COVID-19 patients with elevated glucose levels have promoted cytokine profiles and immune response.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Citocinas/imunologia , Diabetes Mellitus Tipo 2/imunologia , Mediadores da Inflamação/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/virologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo
13.
Eur J Clin Microbiol Infect Dis ; 40(3): 503-513, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32936397

RESUMO

Breast cancer is one of the most common malignant tumors in women. More than half of breast cancer patients are not menopausal at the time of diagnosis. The occurrence and development of premenopausal breast cancer are affected by many factors. Intestinal flora, especially SCFA-producing bacteria, participates in the development of various tumors, and there is a lack of in-depth research in premenopausal breast cancer patients. We used 16S rRNA gene sequencing, targeted metabolomics, and cell culture methods to analyze the changes in the intestinal flora and metabolites of premenopausal breast cancer patients. In addition, we treated breast cancer cells with significantly altered propionate and butyrate in vitro to examine their effects on cell activity. This study followed STROBE guidelines. We found that compared with healthy premenopausal women, the composition and symbiosis of intestinal flora in patients with premenopausal breast cancer changed significantly. The abundance of short-chain fatty acid (SCFA)-producing bacteria was significantly reduced, and the key SCFA-producing enzymes were also significantly reduced. Pediococcus and Desulfovibrio could distinguish premenopausal breast cancer patients from normal premenopausal women. The related propionate and butyrate had a certain ability to inhibit breast cancer cell viability in vitro. As SCFA-producing bacteria, Pediococcus and Desulfovibrio showed potential reference value for the diagnosis of premenopausal breast cancer. The ability of propionate and butyrate to inhibit breast cancer cell lines in vitro suggests that the relevant SCFA receptor may be a new target for the treatment of premenopausal breast cancer.


Assuntos
Neoplasias da Mama/microbiologia , Microbioma Gastrointestinal , Pré-Menopausa , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Butiratos/metabolismo , Butiratos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Propionatos/metabolismo , Propionatos/farmacologia , RNA Ribossômico 16S/genética , Células Tumorais Cultivadas
14.
J Biochem Mol Toxicol ; 35(3): e22668, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33283391

RESUMO

MicroRNA-217 (miR-217) has been recently reported to be abnormally expressed during atherosclerosis. Nonetheless, it still remains unknown whether miR-217 can regulate inflammation, proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) in high-glucose condition. Sprague Dawley rats were used for establishing diabetic animal models. miR-217 mimics and miR-217 inhibitors were transfected into VSMCs. The miR-217 and ROCK1 expressions were measured by quantitative reverse transcription-polymerase chain reaction and Western blot. VSMCs' proliferation, migration, cell cycle, and apoptosis were validated using the Cell Counting Kit-8 assay, Transwell assay, and flow cytometry analysis, respectively. The binding sites between miR-217 and the 3'-untranslated region of ROCK1 were predicted via miRanda, PicTar, TargetScan, and microT databases, and the targeting relationship was confirmed by dual-luciferase reporter experiments. miR-217 was found to be upregulated in VSMCs treated by high glucose and aorta VSMCs of diabetic rats. Transfection of miR-217 mimics significantly induced VSMCs cycle arrest, inhibition of proliferation, reduction of migration, and enhancement of apoptosis. The bioinformatics analysis and dual-luciferase reporter experiments identified ROCK1 as a direct target of miR-217. miR-217 inhibits excessive proliferation and migration of VSMCs induced by high glucose by targeting ROCK1.


Assuntos
Glucose/efeitos adversos , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Glucose/farmacologia , Humanos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Ratos , Ratos Sprague-Dawley
15.
J Diabetes Res ; 2020: 3918723, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062712

RESUMO

People with diabetes have higher risks of various infections. Therefore, these diabetic patients might be at increased risk of COVID-19 and have a poorer prognosis. Up until now, little is known about critical role in the pathogenesis. This study aims to investigate the clinical characteristics of COVID-19 patients with diabetes and secondary hyperglycemia, as well as to explore the purported mechanisms. 80 confirmed COVID-19 subjects were classified into the euglycemia group, secondary hyperglycemia group, and diabetes group. Severity of COVID-19 was defined based on the diagnostic and treatment guideline for SARS-CoV-2 issued by Chinese National Health Committee. According to the severity of the disease, patients of the mild type and common type were registered as mild cases (patients with minimal symptoms and negative CT findings), while patients of the severe type and critical type were enrolled as severe cases (patients with positive CT findings and different extent of clinical manifestations). Patients in the diabetes group were older than those in the euglycemia group, and most of them were male. In the diabetes group, the proportion of severe cases was 57.14%, which was significantly higher than those in the other two groups, and 32% of the COVID-19 patients diagnosed as severe cases were with diabetes. The CD4+ cell counts in the diabetes group were lower than those in the other two groups, while the levels of LDH and hs-CRP were higher. Compared with the euglycemia group, the CD3+ cell counts and the CD4+/CD8+ ratio were decreased, whereas the levels of IL-6 were increased in the secondary hyperglycemia group and diabetes group, with the diversities in the diabetes group being especially more significant. The Spearman correlation analysis revealed that the presence of diabetes was positively correlated with age, hs-CRP, LDH, IL-6, CD8+ cells, and severity of COVID-19 and negatively correlated with CD3+ cell counts, CD4+ cell counts, and CD4+/CD8+ ratio. Compared with the other two groups, the diabetes group exhibited more diverse and multifocal features in CT imagings. Diabetes is a risk factor for influence of the progression and prognosis of COVID-19 due to ongoing inflammation and impaired immune response.


Assuntos
Betacoronavirus/patogenicidade , Glicemia/metabolismo , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 2/imunologia , Hiperglicemia/imunologia , Pneumonia Viral/virologia , Adulto , Idoso , Betacoronavirus/imunologia , Biomarcadores/sangue , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Progressão da Doença , Feminino , Interações Hospedeiro-Patógeno , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
16.
J Diabetes Res ; 2020: 6538208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964054

RESUMO

Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m2), metformin use, and basal metabolic rate (BMR) were obtained from participants' records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all p < 0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 (r = 0.221, p = 0.010), and negative correlations were noted between TSH and BMR (r = -0.618, p < 0.001) and between BMR and FT3 (r = -0.452, p < 0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 (t = 2.468, p = 0.0167) and TSH (t = 2.658, p = 0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina/fisiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/fisiopatologia , Glândula Tireoide/fisiopatologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/sangue , Obesidade/complicações , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
17.
Lipids Health Dis ; 19(1): 199, 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32861247

RESUMO

OBJECTIVE: Recent studies have investigated the circulating adipocyte fatty acid binding protein (FABP4), nesfatin-1, and osteocalcin (OC) concentrations in women diagnosed with gestational diabetes mellitus (GDM), but the findings prove to be conflicting. The objective of this research was to systematically assess the relationship of circulating levels of above adipokines with GDM. METHODS: Pubmed, Embase, Web of Science, Cochrane library, OVID, and Scopus were performed to locate articles published up to January 31, 2020. Pooled standard mean differences (SMDs) with 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated by random-effects models to compare levels of adipokines between GDM cases and control groups. Cumulative and single-arm meta-analyses were also performed. RESULTS: Thirty-one studies comprising 4590 participants were included. No significant differences were found between GDM women and healthy controls in circulating nesfatin-1 levels (4.56 vs. 5.02 ng/mL; SMD = - 0.11, 95% CI -0.61-0.38, 95% PI -1.63-1.41). Nevertheless, circulating FABP4 and OC levels observed in GDM women outnumbered normal controls (FABP4, 23.68 vs. 16.04 ng/mL; SMD = 2.99, 95% CI 2.28-3.69, 95% PI 0.28-5.71; OC, 52.34 vs. 51.04 ng/mL; SMD = 0.68, 95% CI 0.31-1.05, 95% PI -0.48-1.84). The cumulative meta-analysis showed that the SMDs of circulating FABP4 and OC levels had stabilized between the two groups. CONCLUSIONS: Elevated circulating FABP4 and OC levels were observed in GDM women, but nesfatin-1 levels did not change, the PI of OC crossed the no-effect threshold. The results suggested that FABP4 is more suitable as a biomarker of GDM compared to OC in a future study, which is useful in identifying pregnant women who are likely to develop GDM and providing prompt management strategies.


Assuntos
Diabetes Gestacional/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Nucleobindinas/sangue , Osteocalcina/sangue , Feminino , Humanos , Gravidez
18.
Artigo em Inglês | MEDLINE | ID: mdl-32558337

RESUMO

Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the immune system attacking islet cells. T1D, with a long prediabetes period, and the incidence of T1D increases with age during childhood and peaks at 10-14 years. And once it gets overt, it requires lifelong insulin replace treatment. Therefore, the diagnosis of early-stage T1D and effective treatments are important for the management of T1D patients. The imaging methods, such as magnetic resonance imaging (MRI) and so on, were applied in diagnosis of the early stage T1D and its development tracking. The addition of nanomaterials, especially in MRI, can improve the quality of T1D imaging for the diagnosis of T1D at early stage and cause less harm to human body. Meantime, among various treatment options, islet transplantation and immunotherapy are promising, effective, and less independent on insulin. The addition of nanotechnology can effectively reduce the attack of the immune system on drugs and cells, making the therapeutic drug more targeted in the body and prolonging the action time between drugs and cells, thus its addition makes these therapy safer and more efficient. In this review, we attempt to summarize the recent advances in the development of nanotechnology advances of T1D including using nanomaterials for the diagnosis and immunological imaging of T1D, protecting the transplanted islet cells from immune system attack, and delivering relevant molecules to targeted immunocytes. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.

19.
J Pharm Pharmacol ; 72(8): 1101-1109, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32391614

RESUMO

OBJECTIVES: Metformin (MET) has protective effect on diabetic nephropathy (DN). This study aims to demystify the mechanism of MET function in DN. METHODS: Mouse glomerular membrane epithelial cell line SV40-MES-13 was treated with normal or high glucose combined with or without MET. The relationships among H19, miR-143-3p and TGF-ß1 were evaluated by luciferase reporter assay. MTT assay was performed to detect cell proliferation. The levels of inflammatory factors were investigated by enzyme-linked immunosorbent assay. Quantitative real-time PCR and western blot were performed to examine gene and protein expression. KEY FINDINGS: H19 was up-regulated in the SV40-MES-13 cells after treated with high glucose, which was effectively repressed by MET treatment. MET promoted extracellular matrix accumulation, inflammation and proliferation in the SV40-MES-13 cells after treated with high glucose. These influences conferred by MET were abolished by H19 overexpression. H19 regulated TGF-ß1 expression by sponging miR-143-3p. Furthermore, MET inhibited extracellular matrix accumulation, inflammation and proliferation by regulating H19/miR-143-3p/TGF-ß1 axis. CONCLUSIONS: Our studies demonstrated that the protective effect of MET on DN was attributed to the inhibition of proliferation, inflammation and ECM accumulation in mesangial cells via H19/miR-143-3p/TGF-ß1 axis, which suggested that the H19/miR-143-3p/TGF-ß1 axis could be a valuable target for DN therapies.


Assuntos
Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Nefropatias Diabéticas/prevenção & controle , Matriz Extracelular/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Células Mesangiais/efeitos dos fármacos , Metformina/farmacologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Linhagem Celular , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética
20.
Medicine (Baltimore) ; 99(14): e19685, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243407

RESUMO

The effect of intensive insulin therapy on hyperglucagonemia in newly diagnosed type 2 diabetes (T2DM), and its associations with ß-cell function, has not been elucidated. This study assessed the effect of 12 weeks of intensive insulin therapy on hyperglucagonemia in newly diagnosed T2DM and its associations with ß-cell function, with reference to the effects of 12 weeks of oral hypoglycemic agents (OHAs).One hundred eight patients with newly diagnosed T2DM were enrolled from January 2015 to December 2015. The patients were randomly divided to receive, for 12 weeks, either intensive insulin therapy or OHAs. Meal tolerance tests were conducted at baseline before treatment (0 week), at 12 weeks (end of treatment), and 12 months after the initiation of treatment. The levels of glucagon, proinsulin, C-peptide (CP), and blood glucose were measured at timepoints 0, 30, and 120 minutes during the meal tolerance test.Intensive insulin treatment was associated with a decrease in glucagon levels (at 0, 30, and 120 minutes) and proinsulin/CP, and an increase in the insulin-secretion index ΔCP30/ΔG30 and ΔCP120/ΔG120, at 12 weeks and 12 months during the follow-up, compared with the corresponding effects of OHAs. Intensive insulin therapy could reduce but failed to normalize glucagon levels at 12 weeks. There were no correlations between the change of percentages in total area under the curve of glucagon and other glycemic parameters (proinsulin/CP; ΔCP30/ΔG30; or ΔCP120/ΔG120). Patients who received intensive insulin therapy were more likely to achieve their target glycemic goal and remission, compared with those who received OHAs.Short-term intensive insulin therapy facilitates the improvement of both ß-cell and α-cell function in newly diagnosed T2DM mellitus. Decline of ß-cell secretion and concomitant α-cell dysfunction may both be involved in the pathogenesis of T2DM.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Secretoras de Glucagon/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Erros Inatos do Metabolismo dos Carboidratos/sangue , Erros Inatos do Metabolismo dos Carboidratos/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Esquema de Medicação , Feminino , Glucagon/sangue , Glucagon/efeitos dos fármacos , Teste de Tolerância a Glucose , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
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