gaba coordinates with insulin in regulating secretory function in pancreatic ins-1 β-cellsgaba坐标在调节胰岛素分泌功能在胰腺ins-1β-cells.pdfVIP

GABA Coordinates with Insulin in Regulating Secretory Function in Pancreatic INS-1 b-Cells Paul Bansal1,2, Shuanglian Wang3,4, Shenghao Liu1,2, Yun-Yan Xiang3,4, Wei-Yang Lu3,4*, Qinghua Wang1,2* 1 Departments of Physiology and Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada, 2 Division of Endocrinology and Metabolism, The Keenan Research Centre in the Li Ka-Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada, 3 Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada, 4 Robarts Research Institute, University of Western Ontario, London, Ontario, Canada Abstract Pancreatic islet b-cells produce large amounts of c-aminobutyric acid (GABA), which is co-released with insulin. GABA inhibits glucagon secretion by hyperpolarizing a-cells via type-A GABA receptors (GABAARs). We and others recently reported that islet b-cells also express GABA Rs and that activation of GABA Rs increases insulin release. Here we A A investigate the effects of insulin on the GABA-GABAAR system in the pancreatic INS-1 cells using perforated-patch recording. The results showed that GABA produces a rapid inward current and depolarizes INS-1 cells. However, pre-treatment of the cell with regular insulin (1 mM) suppressed the GABA-induced current (IGABA) by 43%. Zinc-free insulin also suppressed IGABA to the same extent of inhibition by regular insulin. The inhibition of IGABA occurs within 30 seconds after application of insulin. The insulin-induced inhibition of IGABA persisted in the presence of PI3-kinase inhibitor, but was abolished upon inhibition of ERK, indicating that i