Assessment of the role of interstitial glucagon in the acute glucose secretory responsiveness of in situ pancreatic β-cells

Karen Moens, Veerle Berger, Jung Mo Ahn, Chris Van Schravendijk, Victor J. Hruby, Daniel Pipeleers, Frans Schuit

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Glucagon is a potent stimulator of insulin release in the presence of a permissive glucose concentration, activating β-cells in vitro via both glucagon- and glucagon-like peptide-1 (GLP-1)-receptors. It is still unclear whether locally released glucagon amplifies the secretory responsiveness of neighboring β-cells in the intact pancreas. The present study investigates this question in the perfused pancreas by examining the effects of antagonists for glucagon receptors ([des-His1,des-Phe6, Glu9]glucagon-NH2, 10 μmol/l) and GLP-1-receptors [exendin-(9-39)-NH2, 1 μmol/l] on the insulin secretory response to glucose. The specificity of both antagonists was demonstrated by their selective interaction with glucagon-receptor signaling in rat hepatocytes and GLP-1-receptor signaling in Chinese hamster lung (CHL) fibroblasts. In purified rat β-cells, the glucagon-receptor antagonist (10 μmol/l) inhibited the effect of 1 nmol/l glucagon upon glucose-induced insulin release by 78 ± 6%. In the perfused rat pancreas, neither of these antagonists inhibited the potent secretory response to 20 mmol/l glucose, although they effectively suppressed the potentiating effect of, respectively, an infusion of glucagon (1 nmol/l) or GLP-1 (1 nmol/l) on insulin release. When endogenous glucagon release was enhanced by isoproterenol (100 nmol/l), no amplification was seen in the simultaneous or subsequent insulin secretory response to glucose. It is concluded that, at least under the present selected conditions, the glucose-induced insulin release by the perfused rat pancreas seems to occur independent of an amplifying glucagon signal from neighboring α-cells.

Original languageEnglish (US)
Pages (from-to)669-675
Number of pages7
Issue number3
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


Dive into the research topics of 'Assessment of the role of interstitial glucagon in the acute glucose secretory responsiveness of in situ pancreatic β-cells'. Together they form a unique fingerprint.

Cite this