| First Author | Longuet C | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 4 | Pages | 1196-205 |
| PubMed ID | 23160527 | Mgi Jnum | J:208604 |
| Mgi Id | MGI:5563754 | Doi | 10.2337/db11-1605 |
| Citation | Longuet C, et al. (2013) Liver-specific disruption of the murine glucagon receptor produces alpha-cell hyperplasia: evidence for a circulating alpha-cell growth factor. Diabetes 62(4):1196-205 |
| abstractText | Glucagon is a critical regulator of glucose homeostasis; however, mechanisms regulating glucagon action and alpha-cell function and number are incompletely understood. To elucidate the role of the hepatic glucagon receptor (Gcgr) in glucagon action, we generated mice with hepatocyte-specific deletion of the glucagon receptor. Gcgr(Hep)(-/-) mice exhibited reductions in fasting blood glucose and improvements in insulin sensitivity and glucose tolerance compared with wild-type controls, similar in magnitude to changes observed in Gcgr(-/-) mice. Despite preservation of islet Gcgr signaling, Gcgr(Hep)(-/-) mice developed hyperglucagonemia and alpha-cell hyperplasia. To investigate mechanisms by which signaling through the Gcgr regulates alpha-cell mass, wild-type islets were transplanted into Gcgr(-/-) or Gcgr(Hep)(-/-) mice. Wild-type islets beneath the renal capsule of Gcgr(-/-) or Gcgr(Hep)(-/-) mice exhibited an increased rate of alpha-cell proliferation and expansion of alpha-cell area, consistent with changes exhibited by endogenous alpha-cells in Gcgr(-/-) and Gcgr(Hep)(-/-) pancreata. These results suggest that a circulating factor generated after disruption of hepatic Gcgr signaling can increase alpha-cell proliferation independent of direct pancreatic input. Identification of novel factors regulating alpha-cell proliferation and mass may facilitate the generation and expansion of alpha-cells for transdifferentiation into beta-cells and the treatment of diabetes. |
