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• W2079057725 endingPage "G111" @default.
• W2079057725 startingPage "G100" @default.
• W2079057725 abstract "The insulin receptor (IR) regulates nutrient uptake and utilization in multiple organs, but its role in the intestinal epithelium is not defined. This study developed a mouse model with villin-Cre (VC) recombinase-mediated intestinal epithelial cell (IEC)-specific IR deletion (VC-IR Δ/Δ ) and littermate controls with floxed, but intact, IR (IR fl/fl ) to define in vivo roles of IEC-IR in mice fed chow or high-fat diet (HFD). We hypothesized that loss of IEC-IR would alter intestinal growth, biomarkers of intestinal epithelial stem cells (IESC) or other lineages, body weight, adiposity, and glucose or lipid handling. In lean, chow-fed mice, IEC-IR deletion did not affect body or fat mass, plasma glucose, or IEC proliferation. In chow-fed VC-IR Δ/Δ mice, mRNA levels of the Paneth cell marker lysozyme ( Lyz) were decreased, but markers of other differentiated lineages were unchanged. During HFD-induced obesity, IR fl/fl and VC-IR Δ/Δ mice exhibited similar increases in body and fat mass, plasma insulin, mRNAs encoding several lipid-handling proteins, a decrease in Paneth cell number, and impaired glucose tolerance. In IR fl/fl mice, HFD-induced obesity increased circulating cholesterol; numbers of chromogranin A (CHGA)-positive enteroendocrine cells (EEC); and mRNAs encoding Chga, glucose-dependent insulinotrophic peptide ( Gip), glucagon ( Gcg), Lyz, IESC biomarkers, and the enterocyte cholesterol transporter Scarb1. All these effects were attenuated or lost in VC-IR Δ/Δ mice. These results demonstrate that IEC-IR is not required for normal growth of the intestinal epithelium in lean adult mice. However, our findings provide novel evidence that, during HFD-induced obesity, IEC-IR contributes to increases in EEC, plasma cholesterol, and increased expression of Scarb1 or IESC-, EEC-, and Paneth cell-derived mRNAs." @default.
• W2079057725 created "2016-06-24" @default.
• W2079057725 creator A5030948779 @default.
• W2079057725 creator A5046546707 @default.
• W2079057725 creator A5052086408 @default.
• W2079057725 creator A5052440858 @default.
• W2079057725 creator A5053689759 @default.
• W2079057725 creator A5073031803 @default.
• W2079057725 creator A5091780294 @default.
• W2079057725 date "2015-01-15" @default.
• W2079057725 modified "2023-10-18" @default.
• W2079057725 title "Deletion of intestinal epithelial insulin receptor attenuates high-fat diet-induced elevations in cholesterol and stem, enteroendocrine, and Paneth cell mRNAs" @default.
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