GLP-1 depolarizes the rat pancreatic beta cell in a Na(+)-dependent manner.
An intestinal hormone glucagon-like-peptide-1 (GLP-1) is a prominent candidate for incretin. In vitro experiment showed (Fridolf and Ahren, Mol. Cell. Endocrinol., 96 (1993) 85-90) that GLP-1 increased both insulin secretion and the efflux of 45Ca2+ in a Na(+)-dependent manner. Further, GLP-1 depolarizes the pancreatic beta cells in the presence of high concentration of glucose. Here, we report the effect of GLP-1 on the membrane potential with a physiological concentration of glucose in perforated patch clamp of primary cultured rat beta cells. 10 nM GLP-1 depolarized the beta cell, which was completely reversed by replacing Na+ with the impermeant molecule N-methyl-D-glucamine (NMDG). The Ca2+ channel blocker, Co2+ suppressed the Ca2+ spikes without hyperpolarizing the cell. GLP-1-induced insulin secretion in perifused islets was also suppressed by a prior replacement of Na+ with NMDG. In addition, GLP-1 slightly augmented the long-lasting Ba2+ current, which was reverted to the control level by a selective inhibitor of protein kinase A, H-89. These results indicate: (i) GLP-1 depolarizes the beta cell by activating the membrane Na+ permeability; (ii) GLP-1 slightly modulates the L-type Ca2+ channel probably through protein kinase A; and (iii) at least in part, these mechanisms may be involved in the insulin secretion induced by GLP-1.
Kato
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Department of Physiology, Gunma University, Maebashi, Japan.
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Tatemoto
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D000818:Animals; D001464:Barium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005934:Glucagon / Q000276:immunology; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008536:Meglumine / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D010187:Pancreatic Hormones / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D013449:Sulfonamides
D002121:Calcium Channel Blockers; D007328:Insulin; D007546:Isoquinolines; D010187:Pancreatic Hormones; D010455:Peptides; D011498:Protein Precursors; D013449:Sulfonamides; D001464:Barium; D008536:Meglumine; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide