論文 - 詳細
| RRC ID | 20917 |
|---|---|
| 著者 | Fukami A, Seino Y, Ozaki N, Yamamoto M, Sugiyama C, Sakamoto-Miura E, Himeno T, Takagishi Y, Tsunekawa S, Ali S, Drucker DJ, Murata Y, Seino Y, Oiso Y, Hayashi Y. |
| タイトル | Ectopic expression of GIP in pancreatic β-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides. |
| ジャーナル | Diabetes |
| Abstract |
Glucagon and glucagon-like peptide-1 (GLP-1) are produced in pancreatic α-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 (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 β-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 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. |
| 巻・号 | 62(2) |
| ページ | 510-8 |
| 公開日 | 2013-2-1 |
| DOI | 10.2337/db12-0294 |
| PII | db12-0294 |
| PMID | 23099862 |
| PMC | PMC3554360 |
| MeSH | Animals Cyclic AMP / antagonists & inhibitors Gastric Inhibitory Polypeptide / biosynthesis* Gastric Inhibitory Polypeptide / genetics Gene Deletion Gene Knock-In Techniques Glucagon-Like Peptide-1 Receptor Glucose Intolerance / genetics Glucose Intolerance / metabolism Glucose Tolerance Test Homeostasis / genetics Homeostasis / physiology Immunohistochemistry Incretins / metabolism Insulin / metabolism* Insulin Secretion Insulin-Secreting Cells / cytology Insulin-Secreting Cells / metabolism* Male Mice Peptide Fragments / metabolism* Proglucagon / analysis Proglucagon / metabolism* Receptors, Gastrointestinal Hormone / genetics Receptors, Glucagon / metabolism |
| IF | 7.72 |
| 引用数 | 18 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02831 |