Cited by 151Pancreatic function and diabetesMetabolism, Diabetes, and CancerDiabetes Management and Research

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Transgenic rescue of insulin receptor–deficient mice

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Okamoto, Haruka, Nakae, Jun, Kitamura, Tadahiro, Park, Byung-Chul, Dragatsis, Ioannis, Accili, Domenico·2004·Journal of Clinical Investigation

DOI 10.1172/jci200421645PMC PMC449751

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Abstract

The role of different tissues in insulin action and their contribution to the pathogenesis of diabetes remain unclear.To examine this question, we have used genetic reconstitution experiments in mice.Genetic ablation of insulin receptors causes early postnatal death from diabetic ketoacidosis.We show that combined restoration of insulin receptor function in brain, liver, and pancreatic β cells rescues insulin receptor knockout mice from neonatal death, prevents diabetes in a majority of animals, and normalizes adipose tissue content, lifespan, and reproductive function.In contrast, mice with insulin receptor expression limited to brain or liver and pancreatic β cells are rescued from neonatal death, but develop lipoatrophic diabetes and die prematurely.These data indicate, surprisingly, that insulin receptor signaling in noncanonical insulin target tissues is sufficient to maintain fuel homeostasis and prevent diabetes.

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Authors: Okamoto, H., Nakae, J., Kitamura, T., Park, B.-C., Dragatsis, I., & Accili, D.
Affiliations: Columbia University Irving Medical Center (US)
Columbia University (US)
Corresponding author: Accili, Domenico
ORCID: Okamoto, Haruka
Kitamura, Tadahiro
Dragatsis, Ioannis
Accili, Domenico
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2004-07-15
Volume: 114
Issue: 2
Pages: 214-223
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200421645
PMC: PMC449751
OpenAlex: W1982060139
Cited by: 151
References: 49
Citations by year: 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 10 · 2012: 14
FWCI: 10.42
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (DK58282, DK63608)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK057539, DK63608, R01DK058282, R37DK058282, DK58282, DK 57539, P30DK063608)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords: insulin receptor, transgenic rescue, diabetic ketoacidosis, neonatal lethality, lipoatrophic diabetes, fuel homeostasis, adipose tissue, pancreatic beta cells, brain insulin signaling, lifespan, reproductive function
MeSH terms: Adipose Tissue, Animals, Animals, Newborn, Body Weight, Brain, Glucose, Insulin, Islets of Langerhans, Liver, Mice, Transgenic, Receptor, Insulin, Tissue Distribution, Signal Transduction, Mice, Knockout, Transgenes, Mice

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Transgenic rescue of insulin receptor–deficient mice

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