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Transgenic rescue of insulin receptor–deficient mice
Open accessAbstract
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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“restoration of insulin signaling to the brain as well prevents the development of diabetes (136).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [136]
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Metadata
- 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
- Venue
- Journal of Clinical Investigation
- Published
- 2004-07-15
- Volume
- 114
- Issue
- 2
- Pages
- 214-223
- ISSN
- 0021-9738 (ISSN-L)
- 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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