G-proteins are important mediators of hormonal inhibition of insulin secretion. To characterize the pertussis toxin–sensitive substrates present in HIT cell membranes, we performed immunoblots with specific antisera and found evidence for the presence of GIα1, GIα2, GIα3, and three forms of GOoα. We observed that pertussis toxin–sensitive substrates mediate all of the effects of SRIF, and a major portion of the effects of EPI, on insulin secretion from rat islets during static incubations. These results agree with our previously reported studies examining phasic glucose-induced insulin secretion from HIT cells. To ascertain whether inhibition of adenylate cyclase, presumably involving coupling of the catalytic subunit to GI, may be a common mechanism for both hormones, we studied the effects of 8-bromo-cyclic AMP and found that this agent partially prevented the inhibitory effects of both hormones. We also observed that the inhibitory effects of SRIF and EPI on insulin were nonadditive, that both hormones were additive to nickel chloride during inhibition of insulin release, and that they noncompetitively inhibited glipizide-induced insulin secretion through pertussis toxin-sensitive mechanisms. Together, these results suggest that both hormones exert their effects on insulin secretion at multiple G- protein -regulated sites including adenylate cyclase and sites distal to the glipizide-binding site on the KATP channel.
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Original Articles|
November 01 1992
G-Proteins and Hormonal Inhibition of Insulin Secretion From HIT-T15 Cells and Isolated Rat Islets
Elizabeth R Seaquist;
Elizabeth R Seaquist
Diabetes Center and Division of Endocrinology, Department of Medicine; and the Department of Pharmacology, University of Minnesota
Minneapolis, Minnesota
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Andrea Robertson Neal;
Andrea Robertson Neal
Diabetes Center and Division of Endocrinology, Department of Medicine; and the Department of Pharmacology, University of Minnesota
Minneapolis, Minnesota
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Kirk D Shoger;
Kirk D Shoger
Diabetes Center and Division of Endocrinology, Department of Medicine; and the Department of Pharmacology, University of Minnesota
Minneapolis, Minnesota
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Timothy F Walseth;
Timothy F Walseth
Diabetes Center and Division of Endocrinology, Department of Medicine; and the Department of Pharmacology, University of Minnesota
Minneapolis, Minnesota
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R Paul Robertson
R Paul Robertson
Diabetes Center and Division of Endocrinology, Department of Medicine; and the Department of Pharmacology, University of Minnesota
Minneapolis, Minnesota
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Address correspondence and reprint requests to Elizabeth R. Seaquist, MD, Diabetes Center and the Division of Endocrinology & Metabolism, Box 101 UMHC, University of Minnesota, Minneapolis, MN 55455.
Diabetes 1992;41(11):1390–1399
Article history
Received:
January 16 1992
Revision Received:
May 07 1992
Accepted:
May 07 1992
PubMed:
1383067
Citation
Elizabeth R Seaquist, Andrea Robertson Neal, Kirk D Shoger, Timothy F Walseth, R Paul Robertson; G-Proteins and Hormonal Inhibition of Insulin Secretion From HIT-T15 Cells and Isolated Rat Islets. Diabetes 1 November 1992; 41 (11): 1390–1399. https://doi.org/10.2337/diab.41.11.1390
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