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  • 1
    Publication Date: 1996-02-02
    Description: Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor (IR). Treatment of cultured murine adipocytes with TNF-alpha was shown to induce serine phosphorylation of insulin receptor substrate 1 (IRS-1) and convert IRS-1 into an inhibitor of the IR tyrosine kinase activity in vitro. Myeloid 32D cells, which lack endogenous IRS-1, were resistant to TNF-alpha-mediated inhibition of IR signaling, whereas transfected 32D cells that express IRS-1 were very sensitive to this effect of TNF-alpha. An inhibitory form of IRS-1 was observed in muscle and fat tissues from obese rats. These results indicate that TNF-alpha induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hotamisligil, G S -- Peraldi, P -- Budavari, A -- Ellis, R -- White, M F -- Spiegelman, B M -- DK 42539/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 2;271(5249):665-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8571133" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/*metabolism ; Adipose Tissue/metabolism ; Animals ; Cells, Cultured ; Insulin/pharmacology ; Insulin Receptor Substrate Proteins ; Insulin Resistance/*physiology ; Male ; Mice ; Muscle, Skeletal/metabolism ; Obesity/*metabolism ; Phosphoproteins/metabolism/*physiology ; Phosphorylation ; Rats ; Rats, Zucker ; Receptor, Insulin/*antagonists & inhibitors/metabolism ; Serine/metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-04-24
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982719/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982719/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zaret, Kenneth S -- White, Morris F -- R01 DK055326/DK/NIDDK NIH HHS/ -- England -- Nature. 2010 Apr 22;464(7292):1132-3. doi: 10.1038/4641132a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20414295" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Death/drug effects ; Cell Differentiation/*physiology ; Cell Lineage ; Cell Proliferation ; Cell Transdifferentiation/*physiology ; Diabetes Mellitus, Type 1/pathology/therapy ; Diphtheria Toxin/pharmacology/toxicity ; Glucagon/biosynthesis/secretion ; Glucagon-Secreting Cells/*cytology/metabolism/secretion ; Humans ; Insulin/biosynthesis/pharmacology/secretion ; Insulin-Secreting Cells/*cytology/drug effects/metabolism/secretion ; Mice ; Mice, Transgenic ; Regeneration/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2007-07-21
    Description: Reduced insulin-like signaling extends the life span of Caenorhabditis elegans and Drosophila. Here, we show that, in mice, less insulin receptor substrate-2 (Irs2) signaling throughout the body or just in the brain extended life span up to 18%. At 22 months of age, brain-specific Irs2 knockout mice were overweight, hyperinsulinemic, and glucose intolerant; however, compared with control mice, they were more active and displayed greater glucose oxidation, and during meals they displayed stable superoxide dismutase-2 concentrations in the hypothalamus. Thus, less Irs2 signaling in aging brains can promote healthy metabolism, attenuate meal-induced oxidative stress, and extend the life span of overweight and insulin-resistant mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taguchi, Akiko -- Wartschow, Lynn M -- White, Morris F -- DK38712/DK/NIDDK NIH HHS/ -- DK55326/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):369-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641201" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Brain/*metabolism ; Circadian Rhythm ; Crosses, Genetic ; Diet ; Female ; Glucose/*metabolism ; *Homeostasis ; Insulin Receptor Substrate Proteins ; Insulin Resistance ; Intracellular Signaling Peptides and Proteins/*metabolism ; *Longevity ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Overweight ; Oxidation-Reduction ; Oxygen Consumption ; Phosphoproteins/*metabolism ; Respiration ; *Signal Transduction ; Superoxide Dismutase/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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