| First Author | Fukami A | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 2 | Pages | 510-8 |
| PubMed ID | 23099862 | Mgi Jnum | J:208608 |
| Mgi Id | MGI:5563758 | Doi | 10.2337/db12-0294 |
| Citation | Fukami A, et al. (2013) Ectopic expression of GIP in pancreatic beta-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides. Diabetes 62(2):510-8 |
| abstractText | Glucagon and glucagon-like peptide-1 (GLP-1) are produced in pancreatic alpha-cells and enteroendocrine L-cells, respectively, in a tissue-specific manner from the same precursor, proglucagon, that is encoded by glucagon gene (Gcg), and play critical roles in glucose homeostasis. Here, we studied glucose homeostasis and beta-cell function of Gcg-deficient mice that are homozygous for a Gcg-GFP knock-in allele (Gcg(gfp/gfp)). The Gcg(gfp/gfp) mice displayed improved glucose tolerance and enhanced insulin secretion, as assessed by both oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT). Responses of glucose-dependent insulinotropic polypeptide (GIP) to both oral and intraperitoneal glucose loads were unexpectedly enhanced in Gcg(gfp/gfp) mice, and immunohistochemistry localized GIP to pancreatic beta-cells of Gcg(gfp/gfp) mice. Furthermore, secretion of GIP in response to glucose was detected in isolated islets of Gcg(gfp/gfp) mice. Blockade of GIP action in vitro and in vivo by cAMP antagonism and genetic deletion of the GIP receptor, respectively, almost completely abrogated enhanced insulin secretion in Gcg(gfp/gfp) mice. These results indicate that ectopic GIP expression in beta-cells maintains insulin secretion in the absence of proglucagon-derived peptides (PGDPs), revealing a novel compensatory mechanism for sustaining incretin hormone action in islets. |
