Insulin inhibits glucagon secretion by the activation of PI3-kinase in In-R1-G9 cells
| Autor: | Hiroyuki Motoshima, Hideki Kishikawa, Eiichi Araki, Kazuaki Yoshizato, Tetsuya Taguchi, K. Matsumoto, Kengo Kaneko, Motoaki Shichiri, Tetsuya Shirotani |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
endocrine system
medicine.medical_specialty Time Factors Endocrinology Diabetes and Metabolism Biology Glucagon Alpha cell Cell Line Wortmannin Islets of Langerhans Phosphatidylinositol 3-Kinases chemistry.chemical_compound Endocrinology Internal medicine Insulin receptor substrate Internal Medicine medicine Animals Insulin Enzyme Inhibitors Phosphorylation Glucagon-like peptide 1 receptor Phosphoinositide-3 Kinase Inhibitors Glucagon secretion General Medicine Phosphoproteins Insulin oscillation Androstadienes Enzyme Activation Kinetics Insulin receptor Gene Expression Regulation chemistry Insulin Receptor Substrate Proteins biology.protein hormones hormone substitutes and hormone antagonists |
| Zdroj: | Diabetes Research and Clinical Practice. 44:83-92 |
| ISSN: | 0168-8227 |
| DOI: | 10.1016/s0168-8227(99)00021-2 |
| Popis: | Intracellular mechanisms through which insulin inhibits glucagon secretion remain to be elucidated in glucagon secreting cells. In this study, we confirmed that, in In-R1-G9 cells, a pancreatic alpha cell line, insulin stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) and activated phosphatidylinositol 3-kinase (PI3-kinase). We further studied, using wortmannin, an inhibitor of PI3-kinase, whether the inhibitory effect of insulin on glucagon secretion was mediated through PI3-kinase pathway in these cells. In static incubation studies, insulin significantly inhibited glucagon secretion at 2, 6 and 12 h, which was completely abolished by pretreatment with wortmannin. In perifusion studies, insulin significantly suppressed glucagon secretion after 10 min, which was also blocked by wortmannin. Insulin also reduced glucagon mRNA at 6 and 12 h but not at 2 h. Wortmannin also abolished insulin-induced reduction of glucagon mRNA. Insulin increased the amount of 85 kDa subunit of PI3-kinase in plasma membrane fraction (PM), with a reciprocal decrease of the kinase in cytosol fraction (CY). Insulin also increased PI3-kinase activity in PM, but not in CY. Our results suggest that insulin suppressed glucagon secretion by inhibiting glucagon release and gene expression. Both actions were mediated by activation of PI3-kinase. Recruitment and activation of PI3-kinase in plasma membrane might be relevant at least in part to insulin-induced inhibition of glucagon release. |
| Databáze: | OpenAIRE |
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