The purpose of this review is to examine the debate concerning ghrelin regulation of insulin secretion, discuss recent studies that have demonstrated expression and regulation of ghrelin in the islet, and speculate whether endogenous ghrelin may have an autocrine-paracrine function within the pancreatic islet.
Ghrelin is a recently identified peptydil hormone that has received significant attention for its potential role in the regulation of appetite, body weight, and energy metabolism. Since its discovery in 1999 as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R), extensive characterization of the physiologic roles of ghrelin has led to new insights into how a gastric hormone is able to coordinate growth hormone regulation with the endocrine control of nutritional homeostasis. A less explored area of study is the role of ghrelin in peripheral tissues. Ghrelin mRNA and protein expression has been reported in the small intestine, colon, liver, kidney, brain, testis, ovary, and pancreas. The functional GHS type 1a receptor also has widespread tissue distribution. Although most plasma ghrelin is secreted from the stomach and small intestine, extensive localization of ghrelin and GHS-R to tissues throughout the body suggests that ghrelin may also have local autocrine-paracrine actions.
The presence of ghrelin and its cognate receptor within the pancreatic islet of embryos and neonates, combined with the close association between ghrelin and insulin regulation, suggests that there may be an important function of ghrelin in the local regulation of insulin secretion within the neonatal islet prior to the establishment of systemic ghrelin regulation of energy metabolism.
aMedical Scientists Training Program and Program in Cell & Developmental Biology, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, USA, and bDepartments of Pediatrics and Cellular and Developmental Biology, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, USA
Lori Sussel is supported by NIH DK061248, DK064146, and DK061422.
Correspondence to Lori Sussel, PhD, Barbara Davis Center, University of Colorado Health Science Center, 4200 E. 9th Avenue, Box B140, Denver, CO 80262, USA
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