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PMID: 353076 Published · ppublish English Journal Article

The roles of intracellular and extracellular Ca++ in glucose-stimulated biphasic insulin release by rat islets.

The Journal of clinical investigation ·Vol. 62 ·No. 2 ·1978-08-00 ·Pages 451-8

Wollheim CB, Kikuchi M, Renold AE, Sharp GW

Abstract

Verapamil, an agent known rapidly to block calcium uptake into islets of Langerhans, has been used to study the roles of intra- and extracellular calcium in the two phases of glucose-induced insulin release. Rates of calcium uptake and insulin release during the first phase were measured simultaneously over 5 min in rat islets after maintenance in tissue culture for 2 days. Rates of (45)Ca(++) efflux and insulin release during the first and second phases were also measured simultaneously under perifusion conditions. For this, islets were loaded with (45)Ca(++) during the entire maintenance period to complete isotopic equilibrium. Under static incubation conditions 5 muM Verapamil had no effect upon Ca(++) uptake or insulin release in the presence of 2.8 mM glucose. By contrast, glucose-stimulated calcium influx was totally abolished without there being any significant effect upon first phase insulin release. Thus first phase insulin release is independent of increased uptake of extracellular calcium. The lack of effect of 5 muM Verapamil blockade on first phase insulin release was confirmed, under perifusion conditions, and was in marked contrast to the observed 55% inhibition of second phase release. (45)Ca(++) efflux was inhibited during both phases of the insulin release response. The results show that increased calcium uptake in response to glucose is not involved in the mechanism of first phase insulin release but is required for the full development and maintenance of the second phase release. It seems possible that intracellular calcium is the major regulatory control for first phase insulin release and that intracellular calcium and increased uptake of extracellular calcium contribute almost equally to the second phase of glucose-induced release.

MeSH Terms
Animals Calcium/metabolism,physiology Glucose/pharmacology In Vitro Techniques Insulin/metabolism Islets of Langerhans/drug effects,metabolism Male Potassium/pharmacology Rats Time Factors Verapamil/pharmacology
Chemicals
Insulin Verapamil Glucose Potassium Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wollheim C B
Kikuchi M
Renold A E
Sharp G W
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53 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI109146
Published
1978-08-00
Pages
451-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC371783
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI109146 PMC Full Text View journal details
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