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The incretins: a link between nutrients and well-being

Published online by Cambridge University Press:  08 March 2007

Rémy Burcelin*
Affiliation:
UMR 5018 CNRS-UPS and IFR 31, Rangueil Hospital, L1 Bldg, BP 84225, Toulouse, 31432 cedex 4, France
*
*Corresponding author: Dr Rémy Burcelin, fax +33 562 17 09 05, email burcelin@toulouse.inserm.fr
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Abstract

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The glucoincretins, glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), are intestinal peptides secreted in response to glucose or lipid intake. Data on isolated intestinal tissues, dietary treatments and knockout mice strongly suggest that GIP and GLP-1 secretion requires glucose and lipid metabolism by intestinal cells. However, incretin secretion can also be induced by non-digestible carbohydrates and involves the autonomic nervous system and endocrine factors such as GIP itself and cholecystokinin. The classical pharmacological approach and the recent use of knockout mice for the incretin receptors have shown that a remarkable feature of incretins is the ability to stimulate insulin secretion in the presence of hyperglycaemia only, hence avoiding any hypoglycaemic episode. This important role is the basis of ongoing clinical trials using GLP-1 analogues. Since most of the data concern GLP-1, we will focus on this incretin. In addition, GLP-1 is involved in glucose sensing by the autonomic nervous system of the hepato-portal vein controlling muscle glucose utilization and indirectly insulin secretion. GLP-1 has been shown to decrease glucagon secretion, food intake and gastric emptying, preventing excessive hyperglycaemia and overfeeding. Another remarkable feature of GLP-1 is its secretion by the brain. Recently, elegant data showed that cerebral GLP-1 is involved in cognition and memory. Experiments using knockout mice suggest that the lack of the GIP receptor prevents diet-induced obesity. Consequently, macronutrients controlling intestinal glucose and lipid metabolism would control incretin secretion and would consequently be beneficial for health. The control of incretin secretion represents a major goal for new therapeutic as well as nutrition strategies for treating and/or reducing the risk of hyperglycaemic syndromes, excessive body weight and thus improvement of well-being.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

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