| Title | Sulfonylureas Uncouple Glucose-dependence for GPR40-mediated Enhancement of Insulin Secretion from INS-1E Cells. | | Author(s) | Yang M, Chisholm JW, Soelaiman S, Shryock JC | | Institution | Biology, Gilead Sciences, Inc., 3172 Porter Drive, Palo Alto, CA 94304, USA. | | Source | Mol Cell Endocrinol 2009 Oct 5. | | Abstract | Activation of GPR40 is reported to enhance insulin secretion in the presence of glucose. We determined whether sulfonylureas could replace glucose for GPR40-mediated enhancement of insulin secretion and investigated underlying mechanisms using INS-1E cells. GW9508, a specific agonist of GPR40, significantly enhanced insulin secretion in the presence of high concentrations of glucose. In contrast, sulfonylureas increased insulin secretion in the absence of glucose. In the presence of sulfonylureas, activation of GPR40 significantly enhanced insulin secretion. The L-type calcium channel (LTCC) activator S-(-)-Bay K8644 also concentration-dependently increased insulin secretion in the absence of glucose. In the presence of 10mumol/L S-(-)-Bay K8644, GW9508 significantly increased insulin secretion. On the other hand, the LTCC blocker nifedipine significantly inhibited insulin secretion mediated by either glucose, glipizide or glucose plus GW9508. Thus, sulfonylureas could replace glucose to support GPR40-mediated enhancement of insulin secretion, whereas blockage of LTCC reduced both glucose and sulfonylurea-mediated insulin secretion. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19815053 |
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