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1.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669133

RESUMO

This study investigated the effects of Tiliacora triandra (Colebr.) Diels aqueous extract (TTE) on hepatic glucose production in hepatocellular carcinoma (HepG2) cells and type 2 diabetic (T2DM) conditions. HepG2 cells were pretreated with TTE and its major constituents found in TTE, epicatechin (EC) and quercetin (QC). The hepatic glucose production was determined. The in vitro data were confirmed in T2DM rats, which were supplemented daily with 1000 mg/kg body weight (BW) TTE, 30 mg/kg BW metformin or TTE combined with metformin for 12 weeks. Results demonstrate that TTE induced copper-zinc superoxide dismutase, glutathione peroxidase and catalase genes, similarly to EC and QC. TTE decreased hepatic glucose production by downregulating phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and increasing protein kinase B and AMP-activated protein kinase phosphorylation in HepG2 cells. These results correlated with the antihyperglycemic, antitriglyceridemic, anti-insulin resistance, and antioxidant activities of TTE in T2DM rats, similar to the metformin and combination treatments. Consistently, impairment of hepatic gluconeogenesis in T2DM rats was restored after single and combined treatments by reducing PEPCK and G6Pase genes. Collectively, TTE could potentially be developed as a nutraceutical product to prevent glucose overproduction in patients with obesity, insulin resistance, and diabetes who are being treated with antidiabetic drugs.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/antagonistas & inibidores , Hipoglicemiantes/farmacologia , Menispermaceae/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Glucose/biossíntese , Células Hep G2 , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Injeções Intraperitoneais , Masculino , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina/administração & dosagem , Células Tumorais Cultivadas , Água/química
2.
Rev Med Liege ; 76(2): 105-110, 2021 Feb.
Artigo em Francês | MEDLINE | ID: mdl-33543856

RESUMO

Endocrine disruptors are chemicals or natural molecules able to interfere with the hormonal system of living organisms. These pollutants can promote the emergence of diseases of the endocrine system in humans or animals. In this publication, we will focus on certain families of endocrine disrupting chemicals that may contribute to the development of type 2 diabetes, a disease whose prevalence is increasing strongly in the world.


Assuntos
Diabetes Mellitus Tipo 2 , Disruptores Endócrinos , Poluentes Ambientais , Animais , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Disruptores Endócrinos/toxicidade , Sistema Endócrino , Poluentes Ambientais/toxicidade , Humanos
3.
Am J Physiol Heart Circ Physiol ; 320(3): H1089-H1101, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33449847

RESUMO

The pathological involvement of anion channels in vascular dysfunction that occurs during type 2 diabetes (T2D) is unclear. Here, we tested the hypothesis that TMEM16A, a calcium-activated chloride (Cl-) channel, contributes to modifications in arterial contractility during T2D. Our data indicate that T2D increased TMEM16A mRNA in arterial smooth muscle cells and total and surface TMEM16A protein in resistance-size cerebral and hindlimb arteries of mice. To examine vascular cell types in which TMEM16A protein increased and the functional consequences of TMEM16A upregulation during T2D, we generated tamoxifen-inducible, smooth muscle cell-specific TMEM16A knockout (TMEM16A smKO) mice. T2D increased both TMEM16A protein and Cl- current density in arterial smooth muscle cells of control (TMEM16Afl/fl) mice. In contrast, T2D did not alter arterial TMEM16A protein or Cl- current density in smooth muscle cells of TMEM16A smKO mice. Intravascular pressure stimulated greater vasoconstriction (myogenic tone) in the arteries of T2D TMEM16Afl/fl mice than in the arteries of nondiabetic TMEM16Afl/fl mice. This elevation in myogenic tone in response to T2D was abolished in the arteries of T2D TMEM16A smKO mice. T2D also reduced Akt2 protein and activity in the arteries of T2D mice. siRNA-mediated knockdown of Akt2, but not Akt1, increased arterial TMEM16A protein in nondiabetic mice. In summary, data indicate that T2D is associated with an increase in TMEM16A expression and currents in arterial smooth muscle cells that produces vasoconstriction. Data also suggest that a reduction in Akt2 function drives these pathological alterations during T2D.NEW & NOTEWORTHY We investigated the involvement of TMEM16A channels in vascular dysfunction during type 2 diabetes (T2D). TMEM16A message, protein, and currents were higher in smooth muscle cells of resistance-size arteries during T2D. Pressure stimulated greater vasoconstriction in the arteries of T2D mice that was abolished in the arteries of TMEM16A smKO mice. Akt2 protein and activity were both lower in T2D arteries, and Akt2 knockdown elevated TMEM16A protein. We propose that a decrease in Akt2 function stimulates TMEM16A expression in arterial smooth muscle cells, leading to vasoconstriction during T2D.


Assuntos
Anoctamina-1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Membro Posterior/irrigação sanguínea , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Vasoconstrição , Animais , Anoctamina-1/deficiência , Anoctamina-1/genética , Artérias/metabolismo , Artérias/fisiopatologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/fisiopatologia , Células HEK293 , Humanos , Resistência à Insulina , Masculino , Potenciais da Membrana , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Estreptozocina , Regulação para Cima
4.
Life Sci ; 271: 119116, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33508297

RESUMO

AIMS: Glycemic variability has been shown to be more harmful in the development of diabetic complication than sustained chronic hyperglycemia. In this present study, we tried to reveal the effects of glycemic variability on cardiac damage in diabetic mice and investigate whether sodium-glucose cotransporter 1 (SGLT1), an important cardiac glucose transporter, functions as an important mediator in the process. MATERIALS AND METHODS: Type 2 diabetes mellitus (DM) mice were induced by a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then glycemic variability in type 2 diabetes mellitus (GVDM) was induced by alternately injecting insulin and glucose to DM mice. In order to determine the roles of SGLT1 in GVDM mice, SGLT1 inhibition was performed using shRNA against SGLT1. The blood glucose level, the cardiac function and myocardial injury were assessed. And the expressions of SGLT1 and the activations of NLRP3/caspase-1 pathway and NF-κB in left ventricular tissues were measured. KEY FINDINGS: The results showed that SGLT1 was highly expressed in heart of GVDM mice compared to control and DM groups, and knockdown of SGLT1 reduced glycemic variability in GVDM mice. Moreover, glycemic variability impaired cardiac function, aggravated cardiac injury and induced NLRP3/caspase-1-mediated inflammatory response and pyroptosis. And knockdown of SGLT1 significantly attenuated the cardiac damages that induced by glycemic variability. SIGNIFICANCE: The results indicated that glycemic variability could cause cardiac damage and induce inflammatory response and pyroptosis of cardiomyocytes in diabetic mice, which could be partially blocked by SGLT1 silence.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Miócitos Cardíacos/metabolismo , Piroptose/fisiologia , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/induzido quimicamente , Dieta Hiperlipídica/efeitos adversos , Técnicas de Inativação de Genes/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Distribuição Aleatória , Transportador 1 de Glucose-Sódio/biossíntese , Transportador 1 de Glucose-Sódio/genética , Estreptozocina/toxicidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-33467592

RESUMO

Type 2 diabetes mellitus (T2DM) is characterised by insulin resistance and eventual pancreatic ß-cell dysfunction, resulting in persistent high blood glucose levels. Endocrine disrupting chemicals (EDCs) such as bisphenol A (BPA) are currently under scrutiny as they are implicated in the development of metabolic diseases, including T2DM. BPA is a pervasive EDC, being the main constituent of polycarbonate plastics. It can enter the human body by ingestion, through the skin, and cross from mother to offspring via the placenta or breast milk. BPA is a xenoestrogen that alters various aspects of beta cell metabolism via the modulation of oestrogen receptor signalling. In vivo and in vitro models reveal that varying concentrations of BPA disrupt glucose homeostasis and pancreatic ß-cell function by altering gene expression and mitochondrial morphology. BPA also plays a role in the development of insulin resistance and has been linked to long-term adverse metabolic effects following foetal and perinatal exposure. Several epidemiological studies reveal a significant association between BPA and the development of insulin resistance and impaired glucose homeostasis, although conflicting findings driven by multiple confounding factors have been reported. In this review, the main findings of epidemiological and functional studies are summarised and compared, and their respective strengths and limitations are discussed. Further research is essential for understanding the exact mechanism of BPA action in various tissues and the extent of its effects on humans at environmentally relevant doses.


Assuntos
Diabetes Mellitus Tipo 2 , Disruptores Endócrinos , Compostos Benzidrílicos/toxicidade , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Fenóis/toxicidade , Gravidez
6.
PLoS One ; 15(12): e0244067, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382732

RESUMO

BACKGROUND: Combination antiretroviral drugs (cARVs) prolong patients' lives but are unfortunately thought to increase complications related to metabolic disorders including type-2 Diabetes Mellitus (DM). We sought to confirm the association of cARVs with type-2 DM and ascertain the extent of this association in a rural South African setting. METHODS: A case-control study of 177 (33.33%) cases with HIV/AIDS and type-2 DM were selected and compared with 354 (66.67%) non-DM HIV/AIDS unmatched controls from a rural district of South Africa's third most populous province (Eastern Cape). Cases were identified from community health centres using the district health information system, and controls were identified using simple random sampling from the same health facilities. Odds Ratios (OR), together with 95% confidence intervals, were calculated for all the univariable and multivariable logistic analyses. RESULTS: This study found that cARVs significantly increased the occurrence of type-2 DM among HIV patients. Patients on protease inhibitors (PIs) were at least 21 times significantly (p<0.0001) more likely to be diabetic than those on the fixed dose combination (FDC); those on stavudine (D4T) and zidovudine (AZT) were 2.45 times and 9.44 times respectively more likely to be diabetic than those on FDC (p<0.05). The odds of diabetes increased by more than three-folds for those who had been on antiretroviral drugs for more than 6 years (p<0.005). CONCLUSION: This study has been able to establish the association between cARVs and type-2 DM. It therefore proposes consideration of the usage of AZT, D4T, lopivavir and ritonavir for the treatment of HIV. The study further proposes more prospective research to test these findings further.


Assuntos
Diabetes Mellitus Tipo 2 , Infecções por HIV , População Rural , Estavudina , Zidovudina , Adulto , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , África do Sul/epidemiologia , Estavudina/administração & dosagem , Estavudina/efeitos adversos , Fatores de Tempo , Zidovudina/administração & dosagem , Zidovudina/efeitos adversos
7.
ACS Appl Mater Interfaces ; 12(50): 55659-55674, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33327053

RESUMO

Diabetic skin ulcer is one of the severe complications of diabetes mellitus, which has a high incidence and may cause death or disability. Platelet-rich plasma (PRP) is widely used in the treatment of diabetic wounds due to the effect of growth factors (GFs) derived from it. However, the relatively short half-life of GFs limits their applications in clinics. In addition, the presence of a large amount of proteases in the diabetic wound microenvironment results in the degradation of GFs, which further impedes angiogenesis and diabetic wound healing. In our study, we fabricated a self-healing and injectable hydrogel with a composite of chitosan, silk fibroin, and PRP (CBPGCTS-SF@PRP) for promoting diabetic wound healing. CBPGCTS-SF@PRP could protect PRP from enzymatic hydrolysis, release PRP sustainably, and enhance the chemotaxis of mesenchymal stem cells. The results showed that it could promote the proliferation of repair cells in vitro. Moreover, it could enhance wound healing by expediting collagen deposition, angiogenesis, and nerve repair in a type 2 diabetic rat model and a rat skin defect model. We hope that this study will offer a new treatment for diabetic nonhealing wounds in clinics.


Assuntos
Materiais Biocompatíveis/farmacologia , Hidrogéis/química , Plasma Rico em Plaquetas/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Benzaldeídos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Quitosana/química , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/patologia , Fibroínas/química , Humanos , Hidrogéis/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Nus , Neovascularização Fisiológica/efeitos dos fármacos , Fibras Nervosas/fisiologia , Plasma Rico em Plaquetas/química , Polietilenoglicóis/química , Ratos , Regeneração/efeitos dos fármacos , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia
8.
Eur J Endocrinol ; 183(6): 619-626, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33105101

RESUMO

Objective: The use of combined hormonal contraceptives (CHCs) worsens glucose tolerance, but the risk for glucose metabolism disorders remains controversial. Design: The study is a prospective longitudinal population-based cohort study. Methods: The study was based on a cohort population that comprised 1879 women born in 1966. At age 46, the women answered a questionnaire on contraceptive use and underwent an oral glucose tolerance test. Glucose metabolism indices were evaluated in current CHC (n = 153), progestin-only contraceptive (POC, n = 842), and non-hormonal contraceptive users (n = 884). Results: In the entire study population, current CHC use was significantly associated with prediabetes (OR: 2.0, 95% CI: 1.3-3.2) and type 2 diabetes (OR: 3.3, 95% CI: 1.1-9.7) compared to non-hormonal contraceptive use. After 5 years of use, the prediabetes risk increased 2.2-fold (95% CI: 1.3-3.7) and type 2 diabetes risk increased 4.5-fold (95% CI: 1.5-13.5). Compared with the current POC use, current CHC use was significantly associated with prediabetes (OR: 1.9, 95% CI: 1.2-3.0). Current POC use was not associated with any glucose metabolism disorders. The results prevailed after adjusting for BMI and socioeconomic status. Conclusions: CHC use in perimenopausal women was associated with a significantly increased risk of glucose metabolism disorders. This association should be considered in women with increased metabolic risk.


Assuntos
Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Transtornos do Metabolismo de Glucose/induzido quimicamente , Estado Pré-Diabético/induzido quimicamente , Adulto , Feminino , Teste de Tolerância a Glucose , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Perimenopausa , Estudos Prospectivos
9.
PLoS One ; 15(8): e0237660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841254

RESUMO

This study evaluated the influence of type 2 diabetes mellitus on bone loss, bone repair and cytokine production in hyperglycemic rats, treated or not with metformin. The animals were distributed as follow: Non-Hyperglycemic (NH), Non Hyperglycemic with Ligature (NH-L), Treated Non Hyperglycemic (TNH), Treated Non Hyperglycemic with Ligature Treated (TNH-L), Hyperglycemic (H), Treated Hyperglycemic (TH), Hyperglycemic with Ligature (H-L), Treated Hyperglycemic with Ligature (TH-L). At 40th day after induction of hyperglycemia, the groups NH-L, TNH-L, H-L, TH-L received a ligature to induce periodontitis. On the 69th, the TNH, TNH-L, TH, TH-L groups received metformin until the end of the study. Bone repair was evaluated at histometric and the expression levels of Sox9, RunX2 and Osterix. Analysis of the ex-vivo expression of TNF-α, IFN-γ, IL-12, IL-4, TGF-ß, IL-10, IL-6 and IL-17 were also evaluated. Metformin partially reverse induced bone loss in NH and H animals. Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis. The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment. Increased ex vivo levels of TNF-α, IL-6, IL-4, IL-10 and IL-17 was observed. Hyperglycemia promoted increased IL-10 levels compared to non-hyperglycemic ones. Treatment of NH with metformin was able to mediate increased levels of TNF-α, IL-10 and IL-17, whereas for H an increase of TNF-α and IL-17 was detected in the 24- or 48-hour after stimulation with LPS. Ligature was able to induce increased levels of TNF-α and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.


Assuntos
Perda do Osso Alveolar/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia/complicações , Metformina/administração & dosagem , Periodontite/prevenção & controle , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/metabolismo , Processo Alveolar/citologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/metabolismo , Processo Alveolar/patologia , Animais , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/genética , Diferenciação Celular/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Osteoblastos/fisiologia , Periodontite/etiologia , Periodontite/metabolismo , Ratos , Estreptozocina/toxicidade , Fatores de Transcrição/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-32599884

RESUMO

OBJECTIVE: To test the hypothesis that cadmium (Cd) exposure is associated with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A two-phase health screening (physical examination and laboratory tests) was conducted in a lead smelter community following a Superfund Cleanup. Participants were African Americans aged >19 years to <89 years. Multiple logistic regression was used to analyze T2DM regressed on blood Cd level and covariates: body mass index (BMI), heavy metals (Ar, Cd, Hg, Pb), duration of residence, age, smoking status, and sex. RESULTS: Of 875 subjects environmentally exposed to Cd, 55 were occupationally exposed to by-products of lead smelting and 820 were community residents. In addition, 109 T2DM individuals lived in the community for an average of 21.0 years, and 766 non-T2DM individuals for 19.0 years. T2DM individuals (70.3%) were >50 years old. Blood Cd levels were higher among T2DM subjects (p < 0.006) compared to non-T2DM individuals. Logistic regression of T2DM status identified significant predictors: Cd level (OR = 1.85; 95% CI: 1.14-2.99, p < 0.01), age >50 years (OR = 3.10; 95% CI: 1.91-5.02, p < 0.0001), and BMI (OR = 1.07; CI: 1.04-1.09, 0.0001). In meta-analysis of 12 prior studies and this one, T2DM risk was OR = 1.09 (95% CI: 1.03-1.15, p < 0.004) fixed effects and 1.22 (95% CI: 1.04-1.44, p < 0.02) random effects. DISCUSSION: Chronic environmental Cd exposure was associated with T2DM in a smelter community, controlling for covariates. T2DM onset <50 years was significantly associated with Cd exposure, but >50 years was not. Meta-analysis suggests that Cd exposure is associated with a small, but significant increased risk for T2DM. Available data suggest Cd exposure is associated with an increased propensity to increased insulin resistance.


Assuntos
Cádmio , Diabetes Mellitus Tipo 2 , Adulto , Cádmio/toxicidade , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Resíduos Industriais , Chumbo , Pessoa de Meia-Idade , Texas/epidemiologia , Adulto Jovem
11.
Clinics (Sao Paulo) ; 75: e1656, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520222

RESUMO

OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet ß-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.


Assuntos
Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Oxigenação Hiperbárica/métodos , Células Secretoras de Insulina , Transplante de Células-Tronco Mesenquimais , Animais , China , Diabetes Mellitus Tipo 2/induzido quimicamente , Humanos , Insulina , Masculino , Células-Tronco Mesenquimais , Camundongos , Ratos , Ratos Sprague-Dawley , Células-Tronco , Dente Decíduo
12.
J Nutr ; 150(7): 1799-1807, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32364230

RESUMO

BACKGROUND: Evidence suggests that the relations between intakes of individual fatty acids and risk of type 2 diabetes (T2D) vary. However, associations between intakes of different cooking oils as sources of fatty acids and incident T2D remain largely unknown. OBJECTIVES: We aimed to evaluate relations between intakes of individual cooking oils and incident T2D in a nationwide Chinese cohort. METHODS: Overall 15,022 Chinese adults aged ≥20 y from the China Health and Nutrition Survey (CHNS) without self-reported T2D at entry in the 1997, 2000, 2004, 2006, or 2009 rounds were followed up until 2011. Consumption of various cooking oils/fats including lard, peanut oil, soybean oil, canola oil, sesame oil, and refined blended plant oil was assessed using 3-d 24-h records in each survey and the cumulative mean intake was calculated. Multivariable-adjusted Cox proportional hazards regression models were constructed to estimate the HRs of T2D. RESULTS: A total of 1014 cases were recorded after a median follow-up of 14 y. The intakes of animal and plant cooking oils/fats were both associated with higher T2D risk. Compared with nonconsumers, multivariable-adjusted HRs and 95% CIs for the highest tertiles were 1.31 (1.03, 1.67) for lard, 1.36 (1.10, 1.66) for peanut oil, 1.14 (0.91, 1.43) for soybean oil, 1.11 (0.87, 1.43) for canola oil, 1.02 (0.79, 1.32) for sesame oil, and 1.42 (1.12, 1.82) for refined blended plant oil. Substituting 1 tablespoon/d (8 g · 2000 kcal-1 · d-1) of soybean oil for the sum of lard, peanut oil, refined blended plant oil, and other plant oils was associated with a 3% (HR: 0.97; 95% CI: 0.95, 0.99) lower risk of T2D. CONCLUSIONS: Intakes of lard, peanut oil, and refined blended plant oil but not soybean oil, canola oil, and sesame oil are associated with higher T2D risk. Reducing the consumption of cooking oils in general may be protective against T2D among the Chinese population.This trial was registered at clinicaltrials.gov as NCT03259321.


Assuntos
Grupo com Ancestrais do Continente Asiático , Culinária , Diabetes Mellitus Tipo 2/induzido quimicamente , Gorduras na Dieta , Óleos Vegetais , Adulto , China , Estudos de Coortes , Dieta , Feminino , Humanos , Masculino
13.
Arch Med Res ; 51(6): 492-503, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32451116

RESUMO

OBJECTIVE: To study whether resolvin D1 (RvD1), a metabolite of docosahexaenoic acid (DHA), prevents NA-STZ-induced type 2 diabetes mellitus (type 2 DM) in vivo and if so, what could be the mechanism of this action. MATERIAL AND METHODS: Single intra-peritoneal (i.p) injection of NA-STZ (175 mg/kg body weight of NA and 65 mg/kg of STZ) was injected simultaneously with RvD1 (60 ng/animal) (injected for 5 consecutive days) to Wistar rats. The effect of RvD1 on plasma glucose levels and apoptotic (Bcl2/Bax) and inflammatory (NF-κB/iNOS) protein expression, plasma lipoxin A4 and BDNF (brain-derived neurotrophic factor) were studied. Protein expressions of PI3k-Akt-mTOR pathway along with histopathological studies of brain were also evaluated. RESULTS: NA-STZ-induced type 2 DM rats showed hyperglycemia, enhanced plasma IL-6/TNF-α (p ≤0.01), reduced plasma BDNF (p ≤0.01) and LXA4 (p ≤0.01) levels and low BDNF in pancreatic, hepatic and brain tissues (p <0.001), which were restored to near normal (p ≤0.01) in RvD1 treated group. RvD1 increased insulin sensitivity by suppressing inflammation (NF-κB/iNOS) (p ≤0.01) and decreasing apoptosis (Bcl2/Bax) and restoring BDNF and LXA4 levels to near normal. RvD1 treatment increased phosphorylation of Akt (Ser473), and subsequent activation (phosphorylation) of downstream signaling molecules of PI3K and mTOR indicating that RvD1 acts through PI3K/Akt/mTOR axis. DISCUSSION: RvD1 is effective in preventing NA-STZ-induced type 2 DM in vivo by suppressing oxidative damage, enhancing the production of anti-inflammatory LXA4 and enhancing neuronal cell survival by augmenting the production of BDNF. Thus, RvD1 may be of benefit not only in preventing diabetes mellitus but also diabetes associated Alzheimer's disease and memory loss.


Assuntos
Anti-Inflamatórios/uso terapêutico , Encéfalo/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Niacinamida/efeitos adversos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose , Diabetes Mellitus Tipo 2/induzido quimicamente , Humanos , Masculino , Ratos , Ratos Wistar
14.
Toxicology ; 441: 152502, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32473187

RESUMO

Cigarette smoking is a well-recognized risk factor for type 2 diabetes (T2DM), and may result in islet ß cell damage and impaired insulin secretion. However, the underlying mechanisms remain largely elusive. In the present study, we demonstrated that nicotine induced premature senescence of pancreatic ß cells in vitro and in vivo. The senescence-associated ß-galactosidase (SA-ß-Gal) assay showed that nicotine exposure induced apparent senescence phenotype of ß-TC-6 cells at an initiating dose of 100 µM and starting from 12 h. In addition, 100 and 500 µM of nicotine exposure altered the expression of senescence marker proteins, such as p16, p19 and p21. Furthermore, we uncovered that the levels of intracellular Ca2+ and reactive oxygen species (ROS) were significantly elevated in ß-TC-6 cells following exposure to 100 and 500 µM nicotine, while calcium channel blocker can reverse this effect. Furthermore, the senescence-inducing phenotype was confirmed in rat insulinoma INS-1 cells at a similar dose range, whereas blockade of nAChRs, calcium and ROS led to apparent impairment of senescence. Finally, we found that administration with 100 and 200 µg/mL nicotine in drinking water for 28 days significantly exacerbated aberrant glucose homeostasis in a mouse model of fat-induced T2DM. Of great intrigue, pancreatic ß cells exhibited significantly enhanced senescence following nicotine administration. Taken together, this study suggests that premature senescence plays a pivotal role in nicotine-triggered ß cell destruction and glucose intolerance, providing a theoretical basis for targeted prevention and treatment of smoking-induced T2DM.


Assuntos
Senescência Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/induzido quimicamente , Células Secretoras de Insulina/efeitos dos fármacos , Nicotina/toxicidade , Animais , Western Blotting , Cálcio/metabolismo , Progressão da Doença , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , beta-Galactosidase/metabolismo
15.
Environ Res ; 186: 109551, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32330771

RESUMO

BACKGROUND: Ambient air pollution has recently been related to type 2 diabetes mellitus (T2DM), a disease that has caused an economic and health burden worldwide. Evidence of an association between air pollution and T2DM was reported in the United States and Europe. However, few studies have focused on the association with high levels of air pollutants in a developing country. OBJECTIVES: We conducted a 12-year cohort study to assess the incidence and mortality of T2DM associated with long-term exposure to PM10, SO2, and NO2. METHODS: A retrospective cohort with participants from four cities in northern China was conducted to assess mortality and incidence of T2DM from 1998 to 2009. Incidence of T2DM was self-reported, and incident intake of an antidiabetic drug or injection of insulin simultaneously and mortality of T2DM was obtained from a family member and double checked against death certificates provided from the local center for disease control and prevention. Individual pollution exposures were the mean concentrations of pollutants estimated from the local environmental monitoring centers over the survival years. Hazard ratios (HRs) were estimated using Cox regression models after adjusting for potential confounding factors. RESULTS: A total of 39 054 participants were recruited into the mortality cohort, among which 59 subjects died from T2DM; 38 529 participants were analyzed in the incidence cohort, and 1213 developed new cases of T2DM. For each 10 µg/m3 increase in PM10, SO2, and NO2, the adjusted HRs and 95% confidence interval (CI) for diabetic incidence were 1.831 (1.778, 1.886), 1.287 (1.256, 1.318), and 1.472 (1.419, 1.528), respectively. Similar results can be observed in the analysis of diabetic mortality with HRs (95% CI) up to 2.260 (1.732, 2.950), 1.130 (1.042, 1.225), and 1.525 (1.280, 1.816), respectively. CONCLUSIONS: Our results suggested that long-term exposure to high levels of PM10, SO2, and NO2 increase risk of incident and mortality of T2DM in China.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus Tipo 2 , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Cidades , Estudos de Coortes , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Europa (Continente) , Humanos , Incidência , Material Particulado/análise , Material Particulado/toxicidade , Estudos Retrospectivos
16.
Environ Res ; 185: 109383, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32224340

RESUMO

BACKGROUND: Environmental factors are believed to account for a substantial burden of type 2 diabetes mellitus (T2DM). Non-persistent environmental pollutants (npEPs) are a group of widely-used chemicals identified as endocrine/metabolic disrupting chemicals and obesogens. The aim of this study was to analyse the potential associations of serum levels of three groups of npEPs with the risk of incident T2DM. METHODS: This is a longitudinal study within a sub-sample of Granada EPIC-Spain cohort (n = 670). We quantified serum concentrations of 7 npEPs: four parabens (Methylparaben (MP) ethylparaben (EP), propylparaben (PP) and butilparaben (BP); two benzophenones: Benzophenone 1 (BP1), Benzophenone 3 (BP3); and Bisphenol A (BPA). Exposure was assessed by means of chemical analyses of serum samples collected at recruitment, and information on potential confounders was gathered by using validated questionnaires at baseline. Follow-up was performed by review of patients' clinical records. Cox Proportional Hazards Models were used for the statistical analyses. RESULTS: Median follow-up time was 23 years. There were 182 (27%) incident T2DM diagnoses in our sub-cohort. MP was the most frequently detected npEP, 88.42% samples above the limit of detection, and BP showed the lowest percentage of detection (19.21%). Those individuals within the fourth PP quartile (0.53-9.24 ng/ml) showed a statistically significant increased risk of T2DM (HR = 1.668 p = 0.012), while BP1 concentrations showed an inverse non-significant trend with the risk. CONCLUSIONS: We evidenced a potential contribution of npEP exposure on T2DM, but no clear trend was observed. However, limitations in relation to exposure estimation might influence our findings and further research is warranted to confirm our results.


Assuntos
Diabetes Mellitus Tipo 2 , Poluentes Ambientais , Neoplasias , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental/análise , Humanos , Estudos Longitudinais , Parabenos/análise , Estudos Prospectivos , Espanha/epidemiologia
17.
J Food Sci ; 85(4): 1307-1318, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32249934

RESUMO

We aimed to investigate) the effects of Aronia melanocarpa berry extract (AMBE) on hepatic insulin resistance and its mechanism at the molecular level in high-fat diet (HFD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were supplemented with AMBE at doses of 100 and 400 mg/kg body weight (bw) daily for 8 weeks. AMBE significantly reduced blood glucose and serum insulin levels and the homeostatic model assessment for insulin resistance score; improved glucose tolerance; increased hepatic glycogen content; and regulated glucose metabolism enzyme activity, including glucokinase, pyruvate kinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in the liver. AMBE also reduced lipid accumulation and oxidative stress along with inflammation in the hepatic tissue of T2DM rats and improved hepatic function. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated by AMBE through the elevation of insulin receptor substrate-2, PI3K, Akt, and glycogen synthase kinase-3ß phosphorylation and glucose transporter 2, which might contribute to the promotion of glycogen synthesis and improvement of hepatic insulin resistance. AMBE shows promise as an ingredient of functional foods for alleviating hepatic insulin resistance in T2DM. PRACTICAL APPLICATION: The extract from the berries of Aronia melanocarpa (Michx.) Elliott (AMBE), with its relatively high content of polyphenolic compounds, has been shown to exert hypoglycemic effects in animal models of diabetes. Our findings support the use of A. melanocarpa as a functional food additive for the alleviation of hepatic insulin resistance and the management of glucose homeostasis in T2DM.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Frutas/química , Fígado/efeitos dos fármacos , Photinia/química , Extratos Vegetais/farmacologia , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Frutas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Proteínas Substratos do Receptor de Insulina , Resistência à Insulina , Fígado/metabolismo , Masculino , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
18.
Environ Res ; 184: 109345, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32172074

RESUMO

BACKGROUND: The body burden of metals and persistent organic pollutants (POPs) is particularly high in populations that rely on fish and other marine species for sustenance. This exposure has been associated with an increased risk of type 2 diabetes, but results remain contrasted. OBJECTIVE: We studied this association in two Indigenous populations of northern Québec (Canada) with markedly different prevalences of diabetes and levels of exposure to POPs and mercury. METHODS: As part of health surveys conducted in 2004-2009, diabetes prevalence and glucose metabolism (glucose, insulin, HOMA-IR, HOMA-B) in non-diabetic fasting adults were assessed using similar protocols in two populations: Inuit from Nunavik (n = 877) and Cree from Eeyou Istchee territory (n = 780). Blood mercury, plasma polychlorinated biphenyls (PCBs), organochlorine (OC) pesticides/metabolites and polybrominated diphenylethers (PBDEs) levels were measured in samples collected at the time of examination. Logistic and linear regressions and restricted cubic splines analyses were conducted adjusting for sex, age, waist circumference, smoking and omega-3 fatty acid content in plasma phospholipids. RESULTS: Diabetes prevalence was higher in Cree (20%) than in Inuit (7%), whereas environmental exposure was 2 to 3-fold greater in Inuit than in Cree participants. In the range of exposure common to the two populations, we observed similar linear increases in the risk of diabetes with increasing contaminant exposure. Among Cree participants, fasting glucose was positively associated with plasma PBDE level, and HOMA-B negatively associated with concentrations of ∑PCBs, dichlorodiphenyldichloroethylene, PBDEs and ∑OC pesticides. Among Inuit participants, a trend towards reduced insulin secretion was observed in association with most contaminants, but the relation was nonlinear (greater reduction at intermediate levels of exposure). A significant increase in fasting glucose levels was observed at elevated blood mercury levels (>16 µg/L). CONCLUSION: The observed association between POPs exposure and diabetes risk in the two populations studied should be confirmed using prospective design. Our results suggest the need for additional research on the physiopathological process through which POPs exposure may induce type 2 diabetes in these Indigenous populations.


Assuntos
Diabetes Mellitus Tipo 2 , Poluentes Ambientais , Mercúrio , Bifenilos Policlorados , Adulto , Animais , Canadá , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Poluentes Ambientais/toxicidade , Glucose , Humanos , Mercúrio/toxicidade , Estudos Prospectivos , Quebeque/epidemiologia
19.
Carbohydr Polym ; 235: 115904, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122473

RESUMO

In vitro digestive conditions were simulated to investigate the digestibility of polysaccharides prepared from squash (SPS). A small amount of free glucose monosaccharide was released after salivary and intestinal digestion due to the breakdown of α-(1 → 4)-glucose linkages and may form SPS or a starch impurity. At the same time, there was no obvious change in molecular weight distribution and reducing sugar content throughout this digestion period, demonstrating that the main structure of SPS was relatively stable under the simulated digestive conditions. Thus, most SPS can be transported intact to the large intestine. In addition, SPS alleviated type 2 diabetes (T2D) in rats. Moreover, the content of short-chain fatty acids (SCFAs) in the colon significantly increased after treatment with SPS. The present research provides insight into the non-digestibility of SPS, and suggests its utility to alleviate T2D by promoting the production of SCFA in the colon.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos Voláteis/biossíntese , Polissacarídeos/metabolismo , Animais , Colo/química , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Ácidos Graxos Voláteis/análise , Intestinos/química , Masculino , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ratos , Ratos Wistar , Saliva/química , Saliva/metabolismo , Estômago/química , Estreptozocina/administração & dosagem
20.
Z Naturforsch C J Biosci ; 75(3-4): 103-112, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32187019

RESUMO

The current study aimed to evaluate the in vivo hypoglycemic potential of Myristica fragrans seed extract co-administered with glimepiride in Swiss albino mice. Computational tools were used to further verify the in vivo findings and to help compare this combination to the glimepiride-pioglitazone combination in terms of the binding affinity of the ligands to their respective target protein receptors and the relative stability of the drug-protein complexes. The effect of the combined therapy was observed both in alloxan- and glucose-induced hyperglycemic Swiss albino mice. The mean fasting blood glucose level of the test groups was measured and statistically evaluated using Student's t test. The combined therapy significantly reduced the blood glucose level in a time-dependent manner compared to glimepiride alone. The binding affinity of glimepiride was found to be -7.6 kcal/mol with sulfonylurea receptor 1 in molecular docking. Conversely, macelignan-peroxisome proliferator-activated receptor (PPAR) α and macelignan-PPAR γ complexes were stabilized with -9.2 and -8.3 kcal/mol, respectively. Molecular dynamic simulation revealed that macelignan-PPAR α and γ complexes were more stable than pioglitazone complexes. The combination shows promise in animal and computer models and requires further trials to provide evidence of its activity in humans.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Lignanas/administração & dosagem , Myristica/química , Compostos de Sulfonilureia/administração & dosagem , Aloxano/efeitos adversos , Animais , Diabetes Mellitus Tipo 2/induzido quimicamente , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Glucose/efeitos adversos , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Lignanas/química , Lignanas/farmacologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , PPAR alfa/metabolismo , PPAR gama/metabolismo , Pioglitazona/administração & dosagem , Pioglitazona/farmacologia , Extratos Vegetais/química , Compostos de Sulfonilureia/química , Compostos de Sulfonilureia/farmacologia , Fatores de Tempo
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