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Dorothy Hodgkin Lecture 2008 Gastric inhibitory polypeptide (GIP) revisited: a new therapeutic target for obesity-diabetes?

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Flatt, Peter (2008) Dorothy Hodgkin Lecture 2008 Gastric inhibitory polypeptide (GIP) revisited: a new therapeutic target for obesity-diabetes? DIABETIC MEDICINE, 25 (7). pp. 759-764. [Journal article]

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DOI: 10.1111/j.1464-5491.2008.02455.x

Abstract

There is increasing realization that gastric inhibitory polypeptide (GIP) has actions outside of the pancreas and gastrointestinal tract. Most significant is the presence of functional GIP receptors on adipocytes and the appreciation that GIP, secreted strongly in response to fat ingestion, plays a role in the translation of excessive amounts of dietary fat into adipocyte tissue stores. Such effects open up the possibility of exploiting GIP receptor antagonism for the treatment of obesity and insulin resistance. This is borne out by studies in high-fat-fed mice or ob/ob mice with either genetic knockout of GIP receptor or chemical ablation of GIP action using the GIP receptor antagonist, (Pro(3))GIP. By causing preferential oxidation of fat, blockade of GIP signalling clears triglyceride deposits from liver and muscle, thereby respectively restoring mechanisms for suppression of hepatic glucose output and cellular glucose uptake. Further studies are needed to determine the applicability of this research to human obesity-diabetes. However, proof of concept is provided by emerging evidence that rapid cure of diabetes in grossly obese subjects undergoing Roux-en-Y bypass surgery is mediated in part by surgical bypass of GIP-secreting K-cells in the upper small intestine.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2912
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 10:03
Last Modified:11 Feb 2010 14:26

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