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Ussar, S. ; Haering, M.-F.* ; Fujisaka, S.* ; Lutter, D. ; Lee, K.Y.* ; Li, N.* ; Gerber, G.K.* ; Bry, L.* ; Kahn, C.R.*

Regulation of glucose uptake and enteroendocrine function by the intestinal epithelial insulin receptor.

Diabetes 66, 886-896 (2017)

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Open Access Green as soon as Postprint is submitted to ZB.

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Insulin receptors (IRs) and IGF-I receptors (IGF-IR) are major regulators of metabolism and cell growth throughout the body; however, their roles in the intestine remain controversial. Here we show that genetic ablation of the IR or IGF-IR in intestinal epithelial cells of mice does not impair intestinal growth or development or the composition of the gut microbiome. However, the loss of IRs alters intestinal epithelial gene expression, especially in pathways related to glucose uptake and metabolism. More importantly, the loss of IRs reduces intestinal glucose uptake. As a result, mice lacking the IR in intestinal epithelium retain normal glucose tolerance during aging compared with controls, which show an age-dependent decline in glucose tolerance. Loss of the IR also results in a reduction of glucose-dependent insulinotropic polypeptide (GIP) expression from enteroendocrine K-cells and decreased GIP release in vivo after glucose ingestion but has no effect on glucagon-like peptide 1 expression or secretion. Thus, the IR in the intestinal epithelium plays important roles in intestinal gene expression, glucose uptake, and GIP production, which may contribute to pathophysiological changes in individuals with diabetes, metabolic syndrome, and other insulin-resistant states.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Growth-factor-i; Gastric-inhibitory Polypeptide; Diabetes-mellitus; Organ-culture; Gut; Absorption; Cell; Proliferation; Transport; Localization

ISSN (print) / ISBN 0012-1797

e-ISSN 1939-327X

Journal Diabetes

Quellenangaben Volume: 66, Issue: 4, Pages: 886-896

Publisher American Diabetes Association

Publishing Place Alexandria, VA.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)