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PMID: 2844166 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Stimulation by glucose of cyclic AMP accumulation in mouse pancreatic islets is mediated by protein kinase C.

The Biochemical journal ·Vol. 253 ·No. 1 ·1988-07-01 ·Pages 229-34

Thams P, Capito K, Hedeskov CJ

Abstract

The mechanism of glucose-stimulated cyclic AMP accumulation in mouse pancreatic islets was studied. In the presence of 3-isobutyl-1-methylxanthine, both glucose and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, enhanced cyclic AMP formation 2.5-fold during 60 min of incubation. Both TPA-stimulated and glucose-stimulated cyclic AMP accumulations were abolished by the omission of extracellular Ca2+. The Ca2+ ionophore A23187 did not affect cyclic AMP accumulation itself, but affected the time course of TPA-induced cyclic AMP accumulation, the effect of A23187 + TPA mimicking the time course for glucose-induced cyclic AMP accumulation. A 24 h exposure to TPA, which depletes islets of protein kinase C, abolished the effects of both TPA and glucose on cyclic AMP production. Both TPA-induced and glucose-induced cyclic AMP productions were inhibited by anti-glucagon antibody, and after pretreatment with this antibody glucose stimulation was dependent on addition of glucagon. Pretreatment of islets with TPA for 10 min potentiated glucagon stimulation and impaired somatostatin inhibition of adenylate cyclase activity in a particulate fraction of islets. Carbamoylcholine, which is supposed to activate protein kinase C in islets, likewise stimulated cyclic AMP accumulation in islets. These observations suggest that glucose stimulates islet adenylate cyclase by activation of protein kinase C, and thereby potentiates the effect of endogenous glucagon on adenylate cyclase.

MeSH Terms
Animals Antibodies/immunology Carbachol/pharmacology Cyclic AMP/metabolism Glucagon/immunology Glucose/pharmacology In Vitro Techniques Islets of Langerhans/drug effects,enzymology,metabolism Male Mice Protein Kinase C/metabolism Stimulation, Chemical Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Antibodies Carbachol Glucagon Cyclic AMP Protein Kinase C Glucose Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Thams P
Department of Biochemistry A, University of Copenhagen, Denmark.
Capito K
Hedeskov C J
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40 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2530229
Published
1988-07-01
Pages
229-34
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1149279
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2530229 PMC Full Text View journal details
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