| First Author | Düfer M | Year | 2012 |
| Journal | Diabetes | Volume | 61 |
| Issue | 6 | Pages | 1479-89 |
| PubMed ID | 22492528 | Mgi Jnum | J:196833 |
| Mgi Id | MGI:5489994 | Doi | 10.2337/db11-0815 |
| Citation | Dufer M, et al. (2012) Bile acids acutely stimulate insulin secretion of mouse beta-cells via farnesoid X receptor activation and K(ATP) channel inhibition. Diabetes 61(6):1479-89 |
| abstractText | Type 2 diabetes mellitus is associated with alterations in bile acid (BA) signaling. The aim of our study was to test whether pancreatic beta-cells contribute to BA-dependent regulation of glucose homeostasis. Experiments were performed with islets from wild-type, farnesoid X receptor (FXR) knockout (KO), and beta-cell ATP-dependent K(+) (K(ATP)) channel gene SUR1 (ABCC8) KO mice, respectively. Sodium taurochenodeoxycholate (TCDC) increased glucose-induced insulin secretion. This effect was mimicked by the FXR agonist GW4064 and suppressed by the FXR antagonist guggulsterone. TCDC and GW4064 stimulated the electrical activity of beta-cells and enhanced cytosolic Ca(2+) concentration ([Ca(2+)](c)). These effects were blunted by guggulsterone. Sodium ursodeoxycholate, which has a much lower affinity to FXR than TCDC, had no effect on [Ca(2+)](c) and insulin secretion. FXR activation by TCDC is suggested to inhibit K(ATP) current. The decline in K(ATP) channel activity by TCDC was only observed in beta-cells with intact metabolism and was reversed by guggulsterone. TCDC did not alter insulin secretion in islets of SUR1-KO or FXR-KO mice. TCDC did not change islet cell apoptosis. This is the first study showing an acute action of BA on beta-cell function. The effect is mediated by FXR by nongenomic elements, suggesting a novel link between FXR activation and K(ATP) channel inhibition. |
