The pancreatic β cell recognition of insulin secretagogues: does cyclic AMP mediate the effect of glucose?

Research output: Contribution to journalArticle

Abstract

Insulin release and the content of cAMP were studied in microdissected pancreatic islets of non inbred ob/ob (obese) mice. In the absence of 3 isobutyl 1 methylxanthine, a phosphodiesterase inhibitor, 20 mM glucose had no effect on cAMP save a very small initial rise detectable by a freeze stop perifusion technique only. However, combined with this methylxanthine, 20 mM glucose produced significant increases of cAMP both in perifused islets and in islets conventionally incubated in closed vials. Glucose shared this capacity to raise the cAMP level with D glyceraldehyde and 1,3 dihydroxyacetone. Isobutylmethylxanthine (0.05-1.0 mM) or 5 μg/ml of cholera toxin, an activator of adenylate cyclase, also increased the islet cAMP level; the effects of the methylxanthine, whether or not combined with cholera toxin, were potentiated by glucose. Isobutylmethylxanthine (0.05-1.0 mM) or 5 μg/ml of cholera toxin potentiated insulin release in response to 20 mM glucose. However, only 0.5-1.0 mM isobutylmethylxanthine stimulated insulin release in the presence of 3 mM glucose, whereas 0.05-0.1 mM isobutylmethylxanthine or 5 μg/ml of cholera toxin had no effect on secretion at the low glucose concentration. These discrepancies between cAMP promoting and insulin releasing activities suggest that glucose does not initiate insulin release by activating the β cell adenylate cyclase. By being metabolized in the β cells, glucose may both create a release initiating signal not identical with cAMP and enhance cAMP formation, leading to potentiation of the effect of the initiator signal.

Details

Authors
External organisations
  • Umeå University
Original languageEnglish
Pages (from-to)3405-3409
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume71
Issue number9
Publication statusPublished - 1974 Jan 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes