GLP-1(7-36) amide stimulates insulin secretion in rat islets: studies on the mode of action - PubMed (original) (raw)

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PMID: 1802486

GLP-1(7-36) amide stimulates insulin secretion in rat islets: studies on the mode of action

T Fridolf et al. Diabetes Res. 1991 Apr.

Abstract

Previously it has been shown that glucagon-like peptide (GLP)-1(7-36)amide stimulates insulin secretion from tumoral RIN m5F cells by activation of adenylate cyclase. However, its mechanism in normal islets is not established. We therefore examined the effects of GLP-1(7-36)amide in isolated, overnight cultured, normal rat islets. GLP-1(7-36)amide (greater than or equal to 10(-9) M) stimulated insulin secretion by augmenting both the efficacy and potency of glucose over a wide dose-range of glucose (3.3-16.7 mM). The first 15 min of GLP-1(7-36)amide-stimulated insulin secretion was independent on extracellular Ca2+, whereas a sustained insulin secretion was seen only in the presence of extracellular Ca2+. Concurrently with this, GLP-1(7-36)amide sustainely stimulated 45Ca(2+)-efflux from prelabelled islets only in the presence of extracellular Ca2+, whereas after removal of extracellular Ca2+, the peptide stimulated only a slight 45Ca(2+)-efflux during the first 15 min. GLP-1(7-36)amide also stimulated 86Rb(+)-efflux from prelabelled islets, but in contrast to 45Ca(2+)-efflux, the 86Rb(+)-efflux was not reduced by removal of extracellular Ca2+. GLP-1(7-36)amide had no influence on 3H-efflux from myo-[2-3H]-inositol prelabelled islets. Moreover, the inhibitor of protein kinase C (PKC), staurosporine, did not affect GLP-1(7-36)amide-stimulated insulin secretion. The results show that the first phase of GLP-1(7-36)amide-stimulated insulin secretion is independent on extracellular Ca2+, whereas the sustained phase of GLP-1(7-36)amide-stimulated insulin secretion requires extracellular Ca2+. In contrast, phosphoinositide hydrolysis and PKC are not involved in the signal transduction pathway stimulated by GLP-1(7-36)amide in normal islets.

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GLP-1(7-36) amide stimulates insulin secretion in rat islets: studies on the mode of action - PubMed (original) (raw)