The Bile Acid Tudca Increases Glucose-induced Insulin Secretion Via The Camp/pka Pathway In Pancreatic Beta Cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Objective. While bile acids are important for the digestion process, they also act as signaling molecules in many tissues, including the endocrine pancreas, which expresses specific bile acid receptors that regulate several cell functions. In this study, we investigated the effects of the conjugated bile acid TUDCA on glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells. Methods. Pancreatic islets were isolated from 90-day-old male mice. Insulin secretion was, measured by radioimmunoassay, protein phosphorylation by western blot, Ca2+ signals by fluorescence microscopy and ATP-dependent K+ (K-ATP) channels by electrophysiology. Results. TUDCA dose-dependently increased GSIS in fresh islets at stimulatory glucose concentrations but remained without effect at low glucose levels. This effect was not associated with changes in glucose metabolism, Ca2+ signals or K-ATP channel activity; however, it was lost in the presence of a cAMP competitor or a PICA inhibitor. Additionally, PKA and CREB phosphorylation were observed after 1-hour incubation with TUDCA. The potentiation of GSIS was blunted by the G alpha stimulatory, G protein subunit-specific inhibitor NF449 and mimicked by the specific TGRS agonist INT-777, pointing to the involvement of the bile acid G protein-coupled receptor TGRS. Conclusion. Our data indicate that TUDCA potentiates GSIS through the cAMP/PKA pathway. (C) 2015 Elsevier Inc. All rights reserved.655463Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP 2013/01318-4]Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico [CNPq 200030/2014-0]Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Spanish Ministerio de Ciencia e Innovacion [BFU2013-42789-P, BFU2011-28358]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic beta-cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Taurine (Tau) is involved in beta (beta)-cell function and insulin action regulation. Here, we verified the possible preventive effect of Tau in high-fat diet (HFD)-induced obesity and glucose intolerance and in the disruption of pancreatic beta-cell morpho-physiology. Weaning Swiss mice were distributed into four groups: mice fed on HFD diet (36 % of saturated fat, HFD group); HTAU, mice fed on HFD diet and supplemented with 5 % Tau; control (CTL); and CTAU. After 19 weeks of diet and Tau treatments, glucose tolerance, insulin sensitivity and islet morpho-physiology were evaluated. HFD mice presented higher body weight and fat depots, and were hyperglycemic, hyperinsulinemic, glucose intolerant and insulin resistant. Their pancreatic islets secreted high levels of insulin in the presence of increasing glucose concentrations and 30 mM K+. Tau supplementation improved glucose tolerance and insulin sensitivity with a higher ratio of Akt phosphorylated (pAkt) related to Akt total protein content (pAkt/Akt) following insulin administration in the liver without altering body weight and fat deposition in HTAU mice. Isolated islets from HTAU mice released insulin similarly to CTL islets. HFD intake induced islet hypertrophy, increased beta-cell/islet area and islet and beta-cell mass content in the pancreas. Tau prevented islet and beta-cell/islet area, and islet and beta-cell mass alterations induced by HFD. The total insulin content in HFD islets was higher than that of CTL islets, and was not altered in HTAU islets. In conclusion, for the first time, we showed that Tau enhances liver Akt activation and prevents beta-cell compensatory morpho-functional adaptations induced by HFD.43417911801Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro [FAPERJ E-26/111.914/2011

Long-term taurine supplementation leads to enhanced hepatic steatosis, renal dysfunction and hyperglycemia in mice fed on a high-fat diet

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO803339351FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçã

Taurine Supplementation Leads To A Disruption In Energy Homeostasis In Menopausal Obese Mice.

803735-74

The effect of taurine supplementation on glucose homeostasis: the role of insulin-degrading enzyme

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO803715724FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçã