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1.
Chem Biol Interact ; 315: 108897, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31726037

RESUMO

Type 2 diabetes mellitus (T2DM) is a disease with a drastically growing worldwide prevalence. It is usually associated with numerous complications of which; diabetic nephropathy (DN); is a main complication of microvasculature and more seriously, a common cause of end-stage renal disease (ESRD). Unfortunately, both the lack of a definitive remedy alongside the economic and the social burden on DN patients enforces considerable impetus for developing alternative therapies. IL-33 is a newly discovered member of the IL-1 cytokine family. IL33/ST2 signaling plays a crucial role in acute and chronic kidney diseases. Calycosin is an isoflavone with reported IL33 signaling inhibitory activity. The present study aimed to investigate if calycosin possess renal protective effect in high-fat diet/STZ-induced T2DM model and to clarify the potential underlying mechanisms. HFD-STZ control rats showed functional and structural renal damage confirmed by increased serum creatinine, blood urea nitrogen and albuminuria associated with marked renal glomerulosclerosis and interstitial fibrosis. Initiation of inflammation, oxidative stress, and fibrosis was evident as depicted by elevated renal levels of IL33/ST2 mRNA as well as increased renal NF-κBp65, TNF-α, IL-1ß, MDA, and TGF-ß contents with suppressed Nrf2 and TAC. Calycosin treatment markedly improved the aforementioned makers of renal injury and dysfunction, modulated IL33/ST2 signaling, inflammatory cytokines, oxidative stress and fibrotic processes. This was accompanied by improvement of T2DM-induced renal ultramicroscopic and histopathological alterations.


Assuntos
Fibrose/tratamento farmacológico , Interleucina-33/metabolismo , Isoflavonas/farmacologia , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Receptores de Interleucina-1/metabolismo , Animais , 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/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fibrose/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Rim/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/farmacologia
2.
Food Chem Toxicol ; 135: 110965, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31743741

RESUMO

Perilla oil (PerO), a natural oil with a high unsaturated fatty acid content derived from the mature seeds of Perilla frutescens, is a homology of medicine and food. The type 2 diabetes mellitus (T2DM) model was successfully established using a high-fat and high-sugar diet combined with a single low-dose of streptozocin (STZ). PerO intervention reduced the levels of fasting blood glucose and the level, size and accumulation of lipid droplets, increased the insulin level and diminished the body weight loss. PerO pretreatment markedly promoted the serum levels of alanine transaminase (ALT) and aspartate transaminase alanine (AST) and inhibited the levels of glucose (GLU), glucose-6-phosphate dehydrogenase (G6PD), triglycerides (TGs) and total cholesterol (TC). Moreover, PerO treatment enhanced the expression of phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and activated the expression of glucose transporter 4 (Glut4) and phospho-AKT serine/threonine kinase (p-AS160) in the liver. Additionally, PerO treatment distinctly decreased the abundance of Aerococcus and facilitated the richness of Alloprevotella in the intestine, as well as accelerated the restoration of the gut microflora diversity. Thus, PerO regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice and may be a potential functional food for diabetic treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina/fisiologia , Transdução de Sinais/efeitos dos fármacos , Ácido alfa-Linoleico/uso terapêutico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Perilla/química , Fosfatidilinositol 3-Quinase/metabolismo , Óleos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estreptozocina
3.
PLoS Med ; 16(12): e1002983, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31815931

RESUMO

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent a new class of oral hypoglycemic agents used in the treatment of type 2 diabetes mellitus. They have a positive effect on the progression of chronic kidney disease, but there is a concern that they might cause acute kidney injury (AKI). METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of the effect of SGLT2is on renal adverse events (AEs) in randomized controlled trials and controlled observational studies. PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov were searched without date restriction until 27 September 2019. Data extraction was performed using a standardized data form, and any discrepancies were resolved by consensus. One hundred and twelve randomized trials (n = 96,722) and 4 observational studies with 5 cohorts (n = 83,934) with a minimum follow-up of 12 weeks that provided information on at least 1 adverse renal outcome (AKI, combined renal AE, or hypovolemia-related events) were included. In 30 trials, 410 serious AEs due to AKI were reported. SGLT2is reduced the odds of suffering AKI by 36% (odds ratio [OR] 0.64 [95% confidence interval (CI) 0.53-0.78], p < 0.001). A total of 1,089 AKI events of any severity (AEs and serious AEs [SAEs]) were published in 41 trials (OR 0.75 [95% CI 0.66-0.84], p < 0.001). Empagliflozin, dapagliflozin, and canagliflozin had a comparable benefit on the SAE and AE rate. AEs related to hypovolemia were more commonly reported in SGLT2i-treated patients (OR 1.20 [95% CI 1.10-1.31], p < 0.001). In the observational studies, 777 AKI events were reported. The odds of suffering AKI were reduced in patients receiving SGLT2is (OR 0.40 [95% CI 0.33-0.48], p < 0.001). Limitations of this study are the reliance on nonadjudicated safety endpoints, discrepant inclusion criteria and baseline hypoglycemic therapy between studies, inconsistent definitions of renal AEs and hypovolemia, varying follow-up times in different studies, and a lack of information on the severity of AKI (stages I-III). CONCLUSIONS: SGLT2is reduced the odds of suffering AKI with and without hospitalization in randomized trials and the real-world setting, despite the fact that more AEs related to hypovolemia are reported.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/induzido quimicamente , Glucosídeos/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
4.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(11): 123-127, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31851183

RESUMO

The more frequent prescription of antipsychotics with high proportion of off label use, in particular for children and adolescents, is seen in many countries, including European Union, United States and Russian Federation. In accordance to current clinical guidelines, second-generation antipsychotics are preferred in clinical practice due to the higher tolerability compared to the first-generation antipsychotics. However, second-generation antipsychotics in children and adolescents, especially in continuous use, are associated with cardiac abnormalities and metabolic disorders, including hyperglycemia, and the risk of type 2 diabetes, weight gain and obesity, an increase in prolactin synthesis and hyperlipidemia. The adverse effects of antipsychotics in children and adolescents determine the need for more balanced approaches to their use, careful monitoring of the safety of treatment and the development of measures to prevent and correct side-effects of these drugs.


Assuntos
Antipsicóticos , Adolescente , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Criança , Diabetes Mellitus Tipo 2/induzido quimicamente , Humanos , Obesidade , Federação Russa , Ganho de Peso
5.
Environ Int ; 133(Pt B): 105213, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31654916

RESUMO

OBJECTIVES: To evaluate the associations between long-term exposure to particulate matter with an aerodynamic diameter ≤1.0 µm and ≤2.5 µm (PM1 and PM2.5), nitrogen dioxide (NO2) and type 2 diabetes prevalence and fasting blood glucose levels in Chinese rural populations. MATERIAL AND METHODS: A total of 39, 259 participants were enrolled in The Henan Rural Cohort study. Questionnaires and medical examination were conducted from July 2015 to September 2017 in rural areas of Henan province, China. Three-year average residential exposure levels of PM1, PM2.5, NO2 for each subject were estimated by a spatiotemporal model. Logistic regression and linear regression models were applied to estimate the associations between PM1, PM2.5, NO2 exposure and type 2 diabetes prevalence and fasting blood glucose levels. RESULTS: The mean 3-year residential exposure concentrations of PM1, PM2.5 and NO2 was 57.4 µg/m3, 73.4 µg/m3 and 39.9 µg/m3, respectively. Higher exposure concentrations of PM1, PM2.5, NO2 by 1 µg/m3 was positively related to a 4.0% (95%CIs: 1.026, 1.054), 6.8% (1.052, 1.084) and 5.0% (1.039, 1.061) increase in odds of type 2 diabetes in the final adjusted models. Besides, a 1 µg/m3 increase of PM1, PM2.5 and NO2 was related to a 0.020 mmol/L (95%CIs: 0.014, 0.026), 0.036 mmol/L (95%CIs: 0.030, 0.042) and 0.030 mmol/L (95%CIs: 0.026, 0.034) mmol/L higher fasting blood glucose levels. CONCLUSIONS: Higher exposure concentrations of air pollutants were positively related to the increased odds of type 2 diabetes, as well as higher fasting blood glucose levels in Chinese rural populations.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/epidemiologia , Jejum , Material Particulado/toxicidade , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/induzido quimicamente , Exposição Ambiental , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Material Particulado/análise , Prevalência , População Rural , Adulto Jovem
6.
Environ Int ; 133(Pt A): 105089, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31654984

RESUMO

BACKGROUND: Previous epidemiological studies, largely conducted in high-income countries and cross-sectional, have suggested a relatively strong association between exposure to dichlorodiphenyldichloroethylene (DDE), a metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), and type 2 diabetes. DDT is widely used in India and the prevalence of type 2 diabetes there is increasing, but the association between these factors has not been explored to date. OBJECTIVE: The objective was to estimate the association of the p,p' isomer of DDE with incident type 2 diabetes in India. METHODS: A nested case-control study was conducted in a representative prospective cohort of adults from two cities in India. Participants were enrolled in 2010-11 (n = 12,271) and followed for annual assessment of chronic diseases including type 2 diabetes. Baseline plasma samples from incident cases of diabetes (n = 193) and sex-city-matched controls (n = 323) were selected for analysis of p,p-DDE. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: At baseline, cases had higher p,p-DDE concentrations: geometric mean (95% CI) 330 (273-399) ng/g lipid compared to 223 (189-262) ng/g lipid among controls. Delhi participants had higher p,p-DDE concentrations: 579 (521-643) ng/g lipid compared to 122 (102-145) ng/g lipid in Chennai. In unadjusted models, being in the highest versus lowest quartile of p,p-DDE was associated with a more than doubling of the odds of diabetes: unadjusted OR (95% CI), 2.30 (1.19, 4.43). However, this effect was no longer significant after adjustment for age: adjusted (95% CI), 0.97 (0.46, 2.06). DISCUSSION: Results suggest that levels of p,p'-DDE in Delhi are exceptionally high, but we did not observe a significant association between p,p-DDE and incident type 2 diabetes. As this is the first study to evaluate this association in India, more studies are needed to inform our understanding of the association in this context, including potential routes of exposure.


Assuntos
DDT/toxicidade , Diabetes Mellitus Tipo 2/induzido quimicamente , Diclorodifenil Dicloroetileno/sangue , Praguicidas/toxicidade , Adulto , Estudos de Casos e Controles , Estudos de Coortes , DDT/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diclorodifenil Dicloroetileno/efeitos adversos , Feminino , Humanos , Incidência , Índia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Praguicidas/sangue , Estudos Prospectivos
7.
Vasc Health Risk Manag ; 15: 419-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632046

RESUMO

Introduction: The increasing blood glucose level due to insulin resistance which occurs in diabetes mellitus (DM) may cause vascular damage. This study aims to prove the effect of the polysaccharide peptide (PsP) Ganoderma lucidum on improving vascular damage through an increase of circulating endothelial cells and circulating endothelial cells (CEC) ratio, decreased H2O2, triglyceride (TG), total cholesterol (TC) and insulin resistance in type 2 DM. Methods: Our study is a true experimental study with randomized posttest control group design that used 35 Wistar rats divided into five groups: normal, control (+) and three groups of different variant PsP doses 50, 150 and 300 mg/kg BW (n=7). Results: By using one-way ANOVA and post-hoc Duncan test, the results show a significant increase of endothelial progenitor cell (EPC) concentration (p=0.000) and ratio EPC:CEC (0.000) by dose-dependent fashion and also reduced CEC concentration (p=0.001), H2O2 (p=0.03), TG (p=0.001), TC (p=0.01) and insulin resistance (p=0.003). Conclusion: In this study, PsP induced endothelial repairing process and reduced the risk factor with 300 mg/kg BW as optimum dose. However, further research on EPC and CEC detection markers is important. Further research on PsP and clinical trial for commercial uses is also needed.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Células Endoteliais/efeitos dos fármacos , Proteoglicanas/farmacologia , Reishi , Remodelação Vascular/efeitos dos fármacos , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/induzido quimicamente , Angiopatias Diabéticas/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Peróxido de Hidrogênio/sangue , Resistência à Insulina , Lipídeos/sangue , Proteoglicanas/isolamento & purificação , Ratos Wistar , Reishi/química , Estreptozocina
8.
Pediatr Endocrinol Rev ; 17(1): 4-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599132

RESUMO

Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes including growth and metabolism. GH promotes anabolic action in all tissues except adipose, where it catabolizes stored fat to release energy for the promotion of growth in other tissues. However, chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation. Hence, a sustained release of high levels of GH contributes significantly to the development of insulin resistance by antagonizing the anti-lipolytic action of insulin. The molecular pathways associated with the lipolytic effect of GH in adipose tissue however, remain elusive. Recent studies have provided molecular insights into GH-induced lipolysis and impairment of insulin signaling. This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Hormônio do Crescimento Humano , Resistência à Insulina , Lipólise , Tecido Adiposo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/farmacologia , Humanos , Lipólise/efeitos dos fármacos
9.
Biomed Res Int ; 2019: 3514574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534958

RESUMO

The immune system is involved in the development of diabetes complications and IgG Fc gamma receptors (FcgRs) are key immune receptors responsible for the effective control of both humoral and innate immunity. We investigated the effects of members of the FcgR superfamily into both the streptozotocin plus high fat-induced type 2 diabetes and high fat diet (HFD) models. FcgRIII-/- diabetic mice and FcgRIIb-/- diabetic mice had elevated levels of serum creatinine compared with wildtype (WT) diabetic mice. Renal histology of diabetic FcgRIII knockout and FcgRIIb knockout mice showed mesangial expansion and GBM thickening; the mechanistic study indicated a higher expression of TGF-ß1, TNF-α, and p-NFκB-p65 compared with wild type mouse. The HFD mouse with FcgRIII knockout or FcgRIIb knockout had increased biochemical and renal injury factors, but oxLDL deposition was higher than in FcgRIII-/- diabetic mice and FcgRIIb-/- diabetic mice. In vitro we further examined the mechanism by which the Fc gamma receptor promoted renal injury and transfected glomerular mesangial cells (GMCs) with FcgRI siRNA attenuated the level of TGF-ß1, TNF-α expression. In summary, FcgRI knockdown downregulated kidney inflammation and fibrosis and FcgRIIb knockout accelerated inflammation, fibrosis, and the anomalous deposition of oxLDL whereas FcgRIII deficiency failed to protect kidney from diabetic renal injury. These observations suggested that FcgRs might represent a novel target for the therapeutic intervention of diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/metabolismo , Receptores de IgG/deficiência , Animais , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Camundongos , Camundongos Knockout , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Rev Med Suisse ; 15(659): 1454-1457, 2019 Aug 21.
Artigo em Francês | MEDLINE | ID: mdl-31436061

RESUMO

Statins are the most commonly prescribed cholesterol-lowering drugs for cardiovascular prevention. Data from randomized clinical trials have shown an increased risk of diabetes mellitus type 2 (DT2) on statin treatment. These findings have been confirmed in genetic Mendelian randomization studies and in observational cohorts. The molecular mechanisms remain partly unknown. The risk of TD2 is higher with high doses of statins and in people with preexisting risk factors for T2D (prediabetes, metabolic syndrome). The cardiovascular benefit of statins overdrive by far the risk of diabetes and the prescription of statins in high risk cardiovascular subjects should not be questioned. Glycaemic monitoring and the adaptation of lifestyle and dietary measures are recommended for subjects at risk of T2D.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco
11.
Nutrients ; 11(9)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438590

RESUMO

Male C57BL/6J mice were used to determine the possible therapeutic effects of our previously described tart cherry extract in a chronic obesity mouse model on metabolic parameters, glucose tolerance, inflammatory mediators, and antioxidant capacity. The control group received standard mouse chow, and the high fat control group was switched to a high fat diet and tap water supplemented with 5% sucrose. The high fat + anthocyanin group received the high fat and sucrose diet, but received the anthocyanin-rich tart cherry extract dissolved in their drinking water. After six weeks, an oral glucose tolerance test was performed, and the water-soluble antioxidant capacity (ACW), superoxide dismutase (SOD) activity, and the plasma levels of insulin, C-peptide, leptin, IL-6, MCP-1, adiponectin and resistin were measured. The high fat diet increased body weight, reduced glucose tolerance, and caused an elevation in leptin, IL-6, MCP-1, and resistin levels. Furthermore, antioxidant capacity was decreased with a significant elevation of SOD activity. Anthocyanin treatment failed to reverse the effects of the high fat diet on body weight and glucose tolerance, but significantly reduced the leptin and IL-6 levels. The tart cherry extract also made a significant enhancement in antioxidant capacity and SOD activity. Our results show that chronic anthocyanin intake has a potential to enhance redox status and alleviate inflammation associated with obesity.


Assuntos
Antocianinas/química , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Obesidade/induzido quimicamente , Extratos Vegetais/farmacologia , Prunus avium/química , Adipocinas , Adiponectina , Animais , Antioxidantes , Diabetes Mellitus Tipo 2/induzido quimicamente , Teste de Tolerância a Glucose , Humanos , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Resistina , Superóxido Dismutase
12.
Acta Diabetol ; 56(12): 1239-1245, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31423559

RESUMO

Immune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare-Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previously known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a glucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.


Assuntos
Pontos de Checagem do Ciclo Celular , Diabetes Mellitus Tipo 2/induzido quimicamente , Imunoterapia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Diabetes Mellitus Lipoatrófica/induzido quimicamente , Diabetes Mellitus Lipoatrófica/epidemiologia , Diabetes Mellitus Lipoatrófica/imunologia , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Humanos , Inibidores de Proteínas Quinases/uso terapêutico
13.
J Diabetes Res ; 2019: 3791061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355292

RESUMO

Type 2 diabetes is a disease with a high global prevalence, characterized by chronic hyperglycemia, insulin resistance, polyphagia, polydipsia, polyuria, and changes in body weight. Animal models have been very useful for the study of this disease and to search for new therapeutic targets that delay, attenuate, or avoid diabetic complications. The purpose of this work was to establish a model of type 2 diabetes and exhibit the majority of the characteristics of the disease. Two-day-old male and female Wistar rats were treated once with streptozotocin (70 or 90 mg/kg body weight). After weaning, they were given a sucrose-sweetened beverage (SSB; sucrose at 10 or 30%) during 7 or 11 weeks; their body weight and food intake were measured daily. With the rats at 14 weeks of age, we determined the following: (a) fasting blood glucose, (b) oral glucose tolerance, and (c) insulin tolerance. We found that the supplementation of sucrose at 10% for 7 weeks in male rats which had previously been given streptozotocin (70 mg/kg) at neonatal stage leads to the appearance of the signs and symptoms of the characteristic of type 2 diabetes in adulthood.


Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Estreptozocina/administração & dosagem , Sacarose/administração & dosagem , Animais , Glicemia , Peso Corporal , Feminino , Teste de Tolerância a Glucose , Hiperglicemia/complicações , Insulina/farmacologia , Resistência à Insulina , Masculino , Ratos , Ratos Wistar
14.
Environ Pollut ; 252(Pt B): 1235-1245, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252121

RESUMO

Previous meta-analyses on associations between air pollution (AP) and type 2 diabetes mellitus (T2DM) were mainly focused on studies conducted in high-income countries. Evidence should be updated by including more recent studies, especially those conducted in low- and middle-income countries. We therefore conducted a systematic review and meta-analysis of epidemiological studies to conclude an updated pooled effect estimates between long-term AP exposure and the prevalence and incidence of T2DM. We searched PubMed, Embase, and Web of Science to identify studies regarding associations of AP with T2DM prevalence and incidence prior to January 2019. A random-effects model was employed to analyze the overall effects. A total of 30 articles were finally included in this meta-analysis. The pooled results showed that higher levels of AP exposure were significantly associated with higher prevalence of T2DM (per 10 µg/m3 increase in concentrations of particles with aerodynamic diameter < 2.5 µm (PM2.5): odds ratio (OR) = 1.09, 95% confidence interval (95%CI): 1.05, 1.13; particles with aerodynamic diameter < 10 µm (PM10): OR = 1.12, 95%CI: 1.06, 1.19; nitrogen dioxide (NO2): OR = 1.05, 95%CI:1.03, 1.08). Besides, higher level of PM2.5 exposure was associated with higher T2DM incidence (per 10 µg/m3 increase in concentration of PM2.5: hazard ratio (HR) = 1.10, 95%CI:1.04, 1.16), while the associations between PM10, NO2 and T2DM incidence were not statistically significant. The associations between AP exposure and T2DM prevalence showed no significant difference between high-income countries and low- and middle-incomes countries. However, different associations were identified between PM2.5 exposure and T2DM prevalence in different geographic areas. No significant differences were found in associations of AP and T2DM prevalence/incidence between females and males, except for the effect of NO2 on T2DM incidence. Overall, AP exposure was positively associated with T2DM. There still remains a need for evidence from low- and middle-income countries on the relationships between AP and T2DM.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental/análise , Material Particulado/análise , Poluentes Atmosféricos/toxicidade , Diabetes Mellitus Tipo 2/induzido quimicamente , Feminino , Humanos , Incidência , Masculino , Dióxido de Nitrogênio/análise , Razão de Chances , Material Particulado/toxicidade , Prevalência
15.
Andrologia ; 51(8): e13313, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31179568

RESUMO

Reproductive dysfunction is one of the diabetes complications. Resveratrol, a polyphenol compound, shows antidiabetic and antioxidant effects. The aim of the present study was to investigate the protective effects of resveratrol on sperm parameters and chromatin quality in experimentally induced type 2 diabetes by streptozotocin and nicotinamide. Forty male adult Wistar rats were grouped into normal control, diabetic control and resveratrol-treated diabetic groups (1, 5 and 10 mg/kg orally treated for 30 days). Type 2 diabetes was induced using a single dose of streptozotocin and nicotinamide by intraperitoneal injection. Then, the different parameters and chromatin condensation of the epididymal extracted spermatozoon were studied using aniline blue (AB), acridine orange (AO) and toluidine blue (TB) staining. The sperm parameters including count, motility and viability had significant reduction in diabetic rats (p < 0.05). Resveratrol increased count, motility and viable spermatozoa relative to the diabetic group (p < 0.05). The mean percentage of AB, AO and TB staining positive spermatozoa was increased in diabetic groups compared to control (p < 0.001) and decreased after treatment with 1 and 5 mg/kg resveratrol (p < 0.001). The results of AO and TB staining showed that resveratrol did not have any beneficial effect on chromatin condensation and denatured DNA at the dose of 10 mg/kg.


Assuntos
Antioxidantes/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Suplementos Nutricionais , Infertilidade Masculina/prevenção & controle , Resveratrol/administração & dosagem , Animais , Cromatina/efeitos dos fármacos , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , DNA/efeitos dos fármacos , DNA/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/induzido quimicamente , Relação Dose-Resposta a Droga , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Masculino , Niacinamida/toxicidade , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Estreptozocina/toxicidade , Resultado do Tratamento
16.
Biol Pharm Bull ; 42(8): 1275-1281, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31155547

RESUMO

Polysaccharide is a key bioactive component of Schisandra chinensis and has significant pharmacological activities. The aim of this study was to evaluate the anti-diabetic effect of acidic polysaccharide from Schisandra chinensis (SCAP). Type 2 diabetic (T2D) rats were developed by giving a high-fat diet (HFD) combined with low-dose streptozotocin (STZ), and administered orally with SCAP (25, 50 mg/kg) for 8 weeks. Fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) in the rat's serum were measured. Oral glucose tolerance test (OGTT) and pathological changes of pancreas were observed. Furthermore, expressions of c-Jun N-terminal kinase (JNK), B-cell lymphoma 2-associated X protein (BAX), B-cell lymphoma 2 (Bcl-2), and Cleaved Caspase-3 in pancreatic islet were detected. The results showed that SCAP decreased FBG, TG, TC, LDL-C and MDA levels, increased insulin, HDL-C levels and SOD activity, improved the pathological changes in pancreatic islet. Furthermore, SCAP inhibited the up-regulation of phosphorylated JNK, BAX and Cleaved Caspase-3 proteins, and increased Bcl-2 protein expression. These data indicate that SCAP has a therapeutic effect in T2D rats, and the mechanism may be related to its protection against ß-cells apoptosis by regulating apoptosis-related proteins expression to alleviate the injury caused by the oxidative stress.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polissacarídeos/farmacologia , Schisandra/química , Animais , Glicemia/efeitos dos fármacos , Caspase 3/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/farmacologia , Jejum , Teste de Tolerância a Glucose , Insulina/sangue , Lipídeos/sangue , MAP Quinase Quinase 4/metabolismo , Masculino , Malondialdeído/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Estreptozocina , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
17.
Ecotoxicol Environ Saf ; 179: 290-300, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31071567

RESUMO

Epidemiological and experimental studies have indicated that ambient fine particulate matter (PM2.5) exposure is associated with the occurrence and development of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). However, the mechanism is not clear yet, and there are few studies to explore the possible prevention measure. In this study, C57BL/6 and db/db mice were exposed to concentrated PM2.5 or filtered air using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 12 weeks. From week 11, some of the mice were assigned to receive a subcutaneous injection of AMPK activator (AICAR). Lipid metabolism, glucose tolerance, insulin sensitivity and energy homeostasis were measured. Meanwhile, the respiratory, systemic and visceral fat inflammatory response was detected. The results showed that PM2.5 exposure induced the impairments of glucose tolerance, insulin resistance, lipid metabolism disorders and disturbances of energy metabolism in both C57BL/6 and db/db mice. These impairments might be consistent with the increased respiratory, circulating and visceral adipose tissue (VAT) inflammatory response, which was characterized by the release of IL-6 and TNF-α in lung, serum and VAT. More importantly, AICAR administration led to the significant enhancement of energy metabolism, elevation of AMPK as well as the decreased IL-6 and TNF-α in VAT of PM2.5-exposed mice, which suggesting that AMPK activation might attenuate the inflammatory responses in VAT via the inhibition of MAPKs and NFκB. The study indicated that exposure to ambient PM2.5 under the concentration which is often seen in some developing countries could induce the occurrence of metabolic disorders in normal healthy mice and exacerbate metabolic disorders in diabetic mice. The adverse impacts of PM2.5 on insulin sensitivity, energy homeostasis, lipid metabolism and inflammatory response were associated with AMPK inhibition. AMPK activation might inhibit PM2.5-induced metabolic disorders via inhibition of inflammatory cytokines release. These findings suggested that AMPK activation is a potential therapy to prevent some of the metabolic disorders attributable to air pollution exposure.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Poluição do Ar/efeitos adversos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Metabolismo Energético/efeitos dos fármacos , Obesidade/induzido quimicamente , Material Particulado/toxicidade , Animais , China , Citocinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Homeostase/efeitos dos fármacos , Exposição por Inalação , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Tamanho da Partícula , Fator de Necrose Tumoral alfa/metabolismo
18.
Biofactors ; 45(4): 495-506, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30937979

RESUMO

Environmental noise is a well-recognized health risk and part of the external exposome-the World Health Organization estimates that 1 million healthy life years are lost annually in Western Europe alone due to noise-related complications, including increased incidence of hypertension, heart failure, myocardial infarction, and stroke. Previous data suggest that noise works through two paired pathways in a proposed reaction model for noise exposure. As a nonspecific stressor, chronic low-level noise exposure can cause a disruption of sleep and communication leading to annoyance and subsequent sympathetic and endocrine stress responses leading to increased blood pressure, heart rate, stress hormone levels, and in particular more oxidative stress, being responsible for vascular dysfunction and representing changes of the internal exposome. Chronic stress generates cardiovascular risk factors on its own such as increased blood pressure, blood viscosity, blood glucose, and activation of blood coagulation. To this end, persistent chronic noise exposure increases cardiometabolic diseases, including arterial hypertension, coronary artery disease, arrhythmia, heart failure, diabetes mellitus type 2, and stroke. The present review discusses the mechanisms of the nonauditory noise-induced cardiovascular and metabolic consequences, focusing on mental stress signaling pathways, activation of the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system, the association of these activations with inflammation, and the subsequent onset of oxidative stress and vascular dysfunction. © 2019 BioFactors, 45 (4):495-506, 2019.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Doença da Artéria Coronariana/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Poluentes Ambientais/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Hipertensão/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Coagulação Sanguínea/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Viscosidade Sanguínea/efeitos dos fármacos , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia
19.
Diabetes Res Clin Pract ; 151: 96-105, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30954511

RESUMO

AIMS: To conduct a meta-analysis of statin-associated type 2 diabetes mellitus (T2D) risk among randomized controlled trials (RCTs) and observational studies (OBSs), excluding studies conducted among secondary prevention populations. METHODS: Studies were identified by searching PubMed (1994-present) and EMBASE (1994-present). Articles had to meet the following criteria: (1) follow-up >one year; (2) >50% of participants free of clinically diagnosed ASCVD; (3) adult participants ≥30 years old; (4) reported statin-associated T2D effect estimates; and (5) quantified precision using 95% confidence interval. Data were pooled using random-effects model. RESULTS: We identified 23 studies (35% RCTs) of n = 4,012,555 participants. OBS participants were on average younger (mean difference = 6.2 years) and had lower mean low-density lipoprotein cholesterol (LDL-C, mean difference = 20.6 mg/dL) and mean fasting plasma glucose (mean difference = 5.2 mg/dL) compared to RCT participants. There was little evidence for publication bias (P > 0.1). However, evidence of heterogeneity was observed overall and among OBSs and RCTs (PCochran = <0.05). OBS designs, younger baseline mean ages, lower LDL-C concentrations, and high proportions of never or former smokers were significantly associated with increased statin-associated T2D risk. CONCLUSIONS: Potentially elevated statin-associated T2D risk in younger populations with lower LDL-C merits further investigation in light of evolving statin guidelines targeting primary prevention populations.


Assuntos
Diabetes Mellitus Tipo 2/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Adulto , Idoso , Heterogeneidade Genética , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
BMJ ; 365: l1204, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971393

RESUMO

OBJECTIVE: To investigate the incidence of new onset type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors (dutasteride or finasteride) for long term treatment of benign prostatic hyperplasia. DESIGN: Population based cohort study. SETTING: UK Clinical Practice Research Datalink (CPRD; 2003-14) and Taiwanese National Health Insurance Research Database (NHIRD; 2002-12). PARTICIPANTS: Men in the CPRD who received dutasteride (n=8231), finasteride (n=30 774), or tamsulosin (n=16 270) were evaluated. Propensity score matching (2:1; dutasteride to finasteride or tamsulosin) produced cohorts of 2090, 3445, and 4018, respectively. In the NHIRD, initial numbers were 1251 (dutasteride), 4194 (finasteride), and 86 263 (tamsulosin), reducing to 1251, 2445, and 2502, respectively, after propensity score matching. MAIN OUTCOMES MEASURE: Incident type 2 diabetes using a Cox proportional hazard model. RESULTS: In the CPRD, 2081 new onset type 2 diabetes events (368 dutasteride, 1207 finasteride, and 506 tamsulosin) were recorded during a mean follow-up time of 5.2 years (SD 3.1 years). The event rate per 10 000 person years was 76.2 (95% confidence interval 68.4 to 84.0) for dutasteride, 76.6 (72.3 to 80.9) for finasteride, and 60.3 (55.1 to 65.5) for tamsulosin. There was a modest increased risk of type 2 diabetes for dutasteride (adjusted hazard ratio 1.32, 95% confidence interval 1.08 to 1.61) and finasteride (1.26, 1.10 to 1.45) compared with tamsulosin. Results for the NHIRD were consistent with the findings for the CPRD (adjusted hazard ratio 1.34, 95% confidence interval 1.17 to 1.54 for dutasteride, and 1.49, 1.38 to 1.61 for finasteride compared with tamsulosin). Propensity score matched analyses showed similar results. CONCLUSIONS: The risk of developing new onset type 2 diabetes appears to be higher in men with benign prostatic hyperplasia exposed to 5α-reductase inhibitors than in men receiving tamsulosin, but did not differ between men receiving dutasteride and those receiving finasteride. Additional monitoring might be required for men starting these drugs, particularly in those with other risk factors for type 2 diabetes.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Hiperplasia Prostática/tratamento farmacológico , Inibidores de 5-alfa Redutase/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Dutasterida/efeitos adversos , Dutasterida/uso terapêutico , Finasterida/efeitos adversos , Finasterida/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Tansulosina/efeitos adversos , Tansulosina/uso terapêutico
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