ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Deletion of intestinal epithelial insulin receptor attenuates high-fat diet-induced elevations in cholesterol and stem, enteroendocrine, and Paneth cell mRNAs.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- Westernized diet related arachidonic acid metabolism expands DNA error-prone growth factor-dependent colonic quiescent stem cells in adolescent mice.Cell death & disease · 2026Article
- Construction of a Multitissue Cell Atlas Reveals Cell-Type-Specific Regulation of Molecular and Complex Phenotypes in Pigs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Disentangling the impact of obesity, diet, host factors, and microbiota on small intestinal antimicrobial peptide expression.Gut microbes · 2025Article
- Cholesterol metabolism on stem cell fate determination: a frontier horizon.Stem cell research & therapy · 2025Review
- Insulin in Myenteric Neurons: Time-Dependent and Regional Changes in Type 1 Diabetic Rats.Cells · 2025Article
- Pancreastatin Inhibition Alters the Colonic Epithelial Cells Profile in a Sex-Dependent Manner.International journal of molecular sciences · 2024Article
- Insulin receptor orchestrates kidney antibacterial defenses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Insulin receptor signaling engages bladder urothelial defenses that limit urinary tract infection.Cell reports · 2024Article
- Gut insulin action protects from hepatocarcinogenesis in diabetic mice comorbid with nonalcoholic steatohepatitis.Nature communications · 2023Article
- Intestinal α-Defensins Play a Minor Role in Modulating the Small Intestinal Microbiota Composition as Compared to Diet.Microbiology spectrum · 2023Article
- Multifaceted involvements of Paneth cells in various diseases within intestine and systemically.Frontiers in immunology · 2023Review
- Expression of a constitutively active insulin receptor in Drosulfakinin (Dsk) neurons regulates metabolism and sleep inBiochemistry and biophysics reports · 2022Article
- Secondary Bile Acids and Tumorigenesis in Colorectal Cancer.Frontiers in oncology · 2022Review
- Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease.World journal of gastroenterology · 2021Review
- High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity.Cell reports · 2021Article
- Obesity and intestinal stem cell susceptibility to carcinogenesis.Nutrition & metabolism · 2021Review
- Does an Apple a Day Also Keep the Microbes Away? The Interplay Between Diet, Microbiota, and Host Defense Peptides at the Intestinal Mucosal Barrier.Frontiers in immunology · 2020Review
- Intestinal Lipid Metabolism Genes Regulated by miRNAs.Frontiers in genetics · 2020Article
- Intraintestinal and Parenteral Administration of an Insulin Analogue Leads to Comparable Activation of Signaling Downstream of the Insulin Receptor in the Small Intestine.Journal of diabetes science and technology · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.