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Diabetes. 2015 May;64(5):1513-21. doi: 10.2337/db14-1176. Epub 2014 Nov 20.

Ghrelin Is a Novel Regulator of GLP-1 Secretion.

Author information

1
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
2
Department of Medicine, University of Toronto, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, Canada.
3
Department of Physiology, University of Toronto, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada p.brubaker@utoronto.ca.

Abstract

GLP-1 is a gastrointestinal L-cell hormone that enhances glucose-stimulated insulin secretion. Hence, strategies that prevent GLP-1 degradation or activate the GLP-1 receptor are used to treat patients with type 2 diabetes. GLP-1 secretion occurs after a meal and is partly regulated by other circulating hormones. Ghrelin is a stomach-derived hormone that plays a key role in whole-body energy metabolism. Because ghrelin levels peak immediately before mealtimes, we hypothesized that ghrelin plays a role in priming the intestinal L-cell for nutrient-induced GLP-1 release. The intraperitoneal injection of ghrelin into mice 15 min before the administration of oral glucose enhanced glucose-stimulated GLP-1 release and improved glucose tolerance, whereas the ghrelin receptor antagonist D-Lys GHRP-6 reduced plasma levels of GLP-1 and insulin and diminished oral glucose tolerance. The ghrelin-mediated improvement in glucose tolerance was lost in mice coinjected with a GLP-1 receptor antagonist as well as in Glp1r(-/-) mice lacking the GLP-1 receptor. The impaired oral glucose tolerance in diet-induced obese mice was also improved by ghrelin preadministration. Importantly, ghrelin directly stimulated GLP-1 release from L-cell lines (murine GLUTag, human NCI-H716) through an extracellular signal-related kinase 1/2-dependent pathway. These studies demonstrate a novel role for ghrelin in enhancing the GLP-1 secretory response to ingested nutrients.

PMID:
25412624
DOI:
10.2337/db14-1176
[Indexed for MEDLINE]
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