| First Author | Chow SZ | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 9 | Pages | 2984-95 |
| PubMed ID | 24812426 | Mgi Jnum | J:229838 |
| Mgi Id | MGI:5754669 | Doi | 10.2337/db13-1121 |
| Citation | Chow SZ, et al. (2014) Glycoprotein 130 receptor signaling mediates alpha-cell dysfunction in a rodent model of type 2 diabetes. Diabetes 63(9):2984-95 |
| abstractText | Dysregulated glucagon secretion accompanies islet inflammation in type 2 diabetes. We recently discovered that interleukin (IL)-6 stimulates glucagon secretion from human and rodent islets. IL-6 family cytokines require the glycoprotein 130 (gp130) receptor to signal. In this study, we elucidated the effects of alpha-cell gp130 receptor signaling on glycemic control in type 2 diabetes. IL-6 family cytokines were elevated in islets in rodent models of this disease. gp130 receptor activation increased STAT3 phosphorylation in primary alpha-cells and stimulated glucagon secretion. Pancreatic alpha-cell gp130 knockout (alphagp130KO) mice showed no differences in glycemic control, alpha-cell function, or alpha-cell mass. However, when subjected to streptozotocin plus high-fat diet to induce islet inflammation and pathophysiology modeling type 2 diabetes, alphagp130KO mice had reduced fasting glycemia, improved glucose tolerance, reduced fasting insulin, and improved alpha-cell function. Hyperinsulinemic-euglycemic clamps revealed no differences in insulin sensitivity. We conclude that in a setting of islet inflammation and pathophysiology modeling type 2 diabetes, activation of alpha-cell gp130 receptor signaling has deleterious effects on alpha-cell function, promoting hyperglycemia. Antagonism of alpha-cell gp130 receptor signaling may be useful for the treatment of type 2 diabetes. |
