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Research Article Free access | 10.1172/JCI105663

A Possible Role for the Adenylcyclase System in Insulin Secretion

W. J. Malaisse, F. Malaisse-Lagae, and D. Mayhew

Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana

‡

This work was performed during the tenure of an International postdoctoral research fellowship of the U. S. Public Health Service, 2 FO 5-TW-865-02.

Address requests for reprints to Dr. W. J. Malaisse, The Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Ind. 46207.

*

Received for publication 20 February 1967 and in revised form 10 July 1967.

This work was supported by grant PHS-AM-7211-02 from the U. S. Public Health Service.

Find articles by Malaisse, W. in: PubMed | Google Scholar

Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana

‡

This work was performed during the tenure of an International postdoctoral research fellowship of the U. S. Public Health Service, 2 FO 5-TW-865-02.

Address requests for reprints to Dr. W. J. Malaisse, The Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Ind. 46207.

*

Received for publication 20 February 1967 and in revised form 10 July 1967.

This work was supported by grant PHS-AM-7211-02 from the U. S. Public Health Service.

Find articles by Malaisse-Lagae, F. in: PubMed | Google Scholar

Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana

‡

This work was performed during the tenure of an International postdoctoral research fellowship of the U. S. Public Health Service, 2 FO 5-TW-865-02.

Address requests for reprints to Dr. W. J. Malaisse, The Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Ind. 46207.

*

Received for publication 20 February 1967 and in revised form 10 July 1967.

This work was supported by grant PHS-AM-7211-02 from the U. S. Public Health Service.

Find articles by Mayhew, D. in: PubMed | Google Scholar

Published November 1, 1967 - More info

Published in Volume 46, Issue 11 on November 1, 1967
J Clin Invest. 1967;46(11):1724–1734. https://doi.org/10.1172/JCI105663.
© 1967 The American Society for Clinical Investigation
Published November 1, 1967 - Version history
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Abstract

A possible role for adenylcyclase in insulin secretion was investigated. Isoproterenol, a predominantly β-adrenergic agent, when mixed with an α-adrenergic blocking agent (phenoxybenzamine), stimulated insulin secretion from pieces of the rat's pancreas in vitro. Theophylline, caffeine, 3′5′-cyclic AMP, glucagon, adrenocorticotropin (ACTH), and thyrotropin (TSH), all of which are thought to act through the adenylcyclase systems in the liver and adipose tissue, also stimulated insulin secretion in vitro; oxytocin and vasopressin, which do not stimulate lipolysis in adipose tissue, were inactive. In all cases, stimulation of insulin secretion could not be detected when glucose was absent or present in only low concentrations (less than 100 mg/100 ml) and was maximal at high levels of glucose (300 mg/100 ml). When pancreatic tissue was obtained from normoglycemic rats and contained no detectable glycogen in the Islets, the stimulant effects of glucose and of theophylline were reduced or abolished by mannoheptulose and 2-deoxyglucose. When tissue was derived from rats infused for 8-10 hr with glucose and contained glycogen, theophylline, even in the absence of glucose, stimulated secretion and this effect was reduced by 2-deoxyglucose but not by mannoheptulose. It is suggested that the β-cell contains an adenylcyclase system through which phosphorylase and possibly phosphofructokinase could be activated; and that insulin secretion could depend upon and be regulated by hormones and other substances which influence the rate at which glycolysis proceeds within the β-cell.

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