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Publication : Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo.

First Author  Bando M Year  2012
Journal  Am J Physiol Endocrinol Metab Volume  302
Issue  4 Pages  E403-8
PubMed ID  22114024 Mgi Jnum  J:184651
Mgi Id  MGI:5425213 Doi  10.1152/ajpendo.00341.2011
Citation  Bando M, et al. (2012) Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo. Am J Physiol Endocrinol Metab 302(4):E403-8
abstractText  Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to approximately 16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic beta-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.
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