Glucagon responses of isolated α cells to glucose, insulin, somatostatin, and leptin

Lijun Chen, Jacques Philippe, Roger H Unger

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Objective: To determine whether glucagon suppression by leptin represents a direct effect on α cells rather than an indirect effect mediated via the hypothalamus. Methods: We devised an in vitro α-cell suppression assay in cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus containing mouse leptin receptors, and they were then incubated with leptin, insulin, or somatostatin in concentrations known to suppress glucagon in vivo. Results: Whereas somatostatin and insulin both suppressed the increase in glucagon secretion stimulated by high levels of glucose, leptin had no such effect. This inability of leptin to suppress glucagon in vitro could signify that it acts indirectly by causing the release of glucagon-suppressing peptides from the hypothalamus or stomach. To search for such a peptide, we studied the effects on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone, neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and Agouti-related peptide that might be involved in the hypothalamic action of leptin. None of these peptides suppressed glucagon at low, normal, or elevated glucose concentrations. Conclusions: If the cultured α cells used faithfully mimic the leptin response of in situ α cells of the diabetic animal, the glucagon-suppressing action of leptin is indirect, but is not mediated by any 1 of the 6 neuropeptides tested.

Original languageEnglish (US)
Pages (from-to)819-825
Number of pages7
JournalEndocrine Practice
Volume17
Issue number5
DOIs
StatePublished - Sep 1 2011

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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