Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway
| Autor: | Nobuhiro Miyamura, Kengo Kaneko, M. Uehara, Motoaki Shichiri, K. Matsumoto, Tetsuya Shirotani, Mikio Todaka, S. Ura, Hideki Kishikawa, Eiichi Araki, S. Isami, S. Motoyoshi |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Monosaccharide Transport Proteins Receptor Bradykinin B2 Endocrinology Diabetes and Metabolism medicine.medical_treatment Molecular Sequence Data Bradykinin Muscle Proteins Deoxyglucose Polymerase Chain Reaction chemistry.chemical_compound Mice Dogs Bradykinin receptor binding Internal medicine Insulin receptor substrate Internal Medicine medicine Adipocytes Animals Humans Bradykinin receptor Phosphorylation Cells Cultured Conserved Sequence DNA Primers Glucose Transporter Type 4 biology Base Sequence Insulin Receptors Bradykinin Biological Transport Phosphoproteins Receptor Insulin IRS1 Insulin receptor Kinetics Endocrinology chemistry Adipose Tissue biology.protein Insulin Receptor Substrate Proteins GLUT4 Signal Transduction |
| Zdroj: | Diabetologia. 39(4) |
| ISSN: | 0012-186X |
| Popis: | It has been suggested that bradykinin stimulates glucose uptake in experiments in vivo and in cultured cells. However, its mechanism has not yet been fully elucidated. In this study, the effects of bradykinin on the insulin signalling pathway were evaluated in isolated dog adipocytes. The bradykinin receptor binding study revealed that dog adipocytes possessed significant numbers of bradykinin receptors (Kd = 83 pmol/l, binding sites = 1.7 x 10(4) site/ cell). Reverse transcription-polymerase chain reaction amplification showed the mRNA specific for bradykinin B2 receptor in the adipocytes. Bradykinin alone did not increase 2-deoxyglucose uptake in adipocytes; however, in the presence of insulin (10(-7) mol/l) it significantly increased 2-deoxyglucose uptake in a dose-dependent manner. Bradykinin also enhanced insulin stimulated GLUT4 translocation from the intracellular fraction to the cell membrane, and insulin induced phosphorylation of the insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in dog adipocytes. The time-course of insulin stimulated phosphorylation of the insulin receptor beta subunit revealed that phosphorylation reached significantly higher levels at 10 min, and stayed at the higher levels until 120 min in the presence of bradykinin, suggesting that bradykinin delayed the dephosphorylation of the insulin receptor. It is concluded that bradykinin could potentiate insulin induced glucose uptake through GLUT4 translocation. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by GLUT4 translocation. |
| Databáze: | OpenAIRE |
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