The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes
Open accessAbstract
The molecular link between obesity and beta cell failure that causes diabetes is difficult to establish. Here we show that a conditional knockout of insulin receptor substrate 2 (Irs2) in mouse pancreas beta cells and parts of the brain--including the hypothalamus--increased appetite, lean and fat body mass, linear growth, and insulin resistance that progressed to diabetes. Diabetes resolved when the mice were between 6 and 10 months of age: functional beta cells expressing Irs2 repopulated the pancreas, restoring sufficient beta cell function to compensate for insulin resistance in the obese mice. Thus, Irs2 signaling promotes regeneration of adult beta cells and central control of nutrient homeostasis, which can prevent obesity and diabetes in mice.
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“mice with neuron-specific deletion of either the insulin receptor (IR) or insulin receptor-substrate-2 (IRS-2) are characterized by mild obesity and insulin resistance (27, 97, 105).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [105]
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Type 2 Diabetes-a Matter of ß-Cell Life and Death?
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Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841
Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans
Kullmann, S., Heni, M., Hallschmid, M., Fritsche, A., Preissl, H., & Häring, H.-U. (2016) · Physiological Reviews · doi:10.1152/physrev.00032.2015 · Cited by 622
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Metadata
- Authors
- Lin, X., Taguchi, A., Park, S., Kushner, J. A., Li, F., Li, Y., & White, M. F.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- White, Morris F.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-10-01
- Volume
- 114
- Issue
- 7
- Pages
- 908-916
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC518668
- OpenAlex
- W1966373813
- Cited by
- 313
- References
- 60
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 2 · 2022: 7 · 2021: 11 · 2020: 11 · 2019: 10 · 2018: 8 · 2017: 10 · 2016: 13 · 2015: 22 · 2014: 16 · 2013: 17 · 2012: 14
- FWCI
- 21.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK55236)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin receptor substrate 2, pancreatic beta cells, hypothalamus, obesity, diabetes mellitus, insulin resistance, beta cell regeneration, appetite, nutrient homeostasis, conditional knockout
- MeSH terms
- Animals, Body Weight, Brain, Diabetes Mellitus, Type 2, Diet, Eating, Gene Expression Regulation, Glucose, Homeostasis, Humans, Hypothalamus, Insulin, Insulin Resistance, Islets of Langerhans, Male, Mice, Inbred C57BL, Obesity, Phosphoproteins, Random Allocation, Signal Transduction, Gene Deletion, Mice, Knockout, Intracellular Signaling Peptides and Proteins, Mice, Insulin Receptor Substrate Proteins
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- The paper
- Lin, X., Taguchi, A., Park, S., Kushner, J. A., Li, F., Li, Y., & White, M. F. (2004). Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes. Journal of Clinical Investigation. https://doi.org/10.1172/jci22217
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
