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- Title
Ectopic Expression of GIP in Pancreatic β-Cells Maintains Enhanced Insulin Secretion in Mice With Complete Absence of Proglucagon-Derived Peptides.
- Authors
Fukami, Ayako; Seino, Yusuke; Ozaki, Nobuaki; Yamamoto, Michiyo; Sugiyama, Chisato; Sakamoto-Miura, Eriko; Himeno, Tatsuhito; Takagishi, Yoshiko; Tsunekawa, Shin; Ali, Safina; Drucker, Daniel J.; Murata, Yoshiharu; Seino, Yutaka; Oiso, Yutaka; Hayashi, Yoshitaka
- Abstract
Glucagon and glucagon-like peptide-1 (GLP-1) are produced in pancreatic a-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 β-cell function of Gcg-deficient mice that are homozygous for a Gcg-GFP knock-in allele (Gcggfp/gfp). The Gcggfp/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 Gcggfp/gfp mice, and immunohistochemistry localized GIP to pancreatic β-cells of Gcggfp/gfp mice. Furthermore, secretion of GIP in response to glucose was detected in isolated islets of Gcggfp/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 Gcggfp/gfp mice. These results indicate that ectopic GIP expression in β-cells maintains insulin secretion in the absence of proglucagon-derived peptides (PGDPs), revealing a novel compensatory mechanism for sustaining incretin hormone action in islets.
- Subjects
GLUCAGON-like peptide 1; HYPOGLYCEMIC agents; GLUCAGON-like peptides; PROGLUCAGON; GLUCOSE tolerance tests; LABORATORY mice
- Publication
Diabetes, 2013, Vol 62, Issue 2, p510
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db12-0294