title: Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo.
abstract: 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 ∼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 β-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.
authors: Ghrelin Research Project, Translational Research Center, Kyoto University Hospital, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Mika
authors: M
authors: Bando
authors: Hiroshi
authors: H
authors: Iwakura
authors: Hiroyuki
authors: H
authors: Ariyasu
authors: Hiroshi
authors: H
authors: Hosoda
authors: Go
authors: G
authors: Yamada
authors: Kiminori
authors: K
authors: Hosoda
authors: Souichi
authors: S
authors: Adachi
authors: Kazuwa
authors: K
authors: Nakao
authors: Kenji
authors: K
authors: Kangawa
authors: Takashi
authors: T
authors: Akamizu
mesh_terms: D000217:Acyltransferases / Q000096:biosynthesis; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D054439:Ghrelin / Q000096:biosynthesis* / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D008565:Membrane Proteins; D000217:Acyltransferases; C526983:Mboat4 protein, mouse; D005947:Glucose