biostudies-literatureUssar SNIDDK NIH HHSNational Institutes of Health886-896https://www.ebi.ac.uk/biostudies/studies/S-EPMC5360299biostudies-literatureUnknown66(4)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 reductiDiabetesRegulation of Glucose Uptake and Enteroendocrine Function by the Intestinal Epithelial Insulin Receptor.PMC5360299T32 DK007260R01 DK033201P30-DK-036836P30-DK-034854DK-36836P30 DK036836P30 DK034854R37 DK031036DK-31036R01 DK031036Haering MFBry LKahn CRUssar SFujisaka SLutter DLee KYLi NGerber GKfalseRegulation of Glucose Uptake and Enteroendocrine Function by the Intestinal Epithelial Insulin Receptor.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 reducti2017-01-01T00:00:00Z2017 Apr2025-04-04T12:38:51.169Z2019-03-26T23:22:07ZS-EPMC53602992809625810.2337/db15-1349