Anchoring of protein kinase A facilitates hormone-mediated insulin secretion

Linda B. Lester, Lorene K. Langeberg, John D. Scott

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Impaired insulin secretion is a characteristic of non-insulin-dependent diabetes mellitus (NIDDM). One possible therapeutic agent for NIDDM is the insulinotropic hormone glucagon-like peptide 1 (GLP-1). GLP-1 stimulates insulin secretion through several mechanisms including activation of protein kinase A (PKA). We now demonstrate that the subcellular targeting of PKA through association with A-kinase-anchoring proteins (AKAPs) facilitates GLP- 1-mediated insulin secretion. Disruption of PKA anchoring by the introduction of anchoring inhibitor peptides or expression of soluble AKAP fragments blocks GLP-1 action in primary islets and cAMP-responsive insulin secretion in clonal beta cells (RINm5F). Displacement of PKA also prevented cAMP- mediated elevation of intracellular calcium suggesting that localized PKA phosphorylation events augment calcium flux.

Original languageEnglish (US)
Pages (from-to)14942-14947
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number26
DOIs
StatePublished - Dec 23 1997

ASJC Scopus subject areas

  • General

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