| Thyroid hormone potentiates insulin signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes. | |
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MedLine Citation:
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PMID: 20883475 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: The thyroid hormone, triiodothyronine (T3) has many metabolic functions. Unexpectedly, exogenous T3 lowered blood glucose in db/db mice, a model of type 2 diabetes. Here, we have explored this finding and its possible mechanisms further. EXPERIMENTAL APPROACH: db/db and lean mice were treated with T3, the phosphoinositide 3- kinase (PI3-kinase) inhibitor, LY294002, plus T3, or vehicles. Blood glucose, insulin sensitivity, levels and synthesis were measured. Effects of T3 on intracellular insulin signaling were analyzed in 3T3-L1 pre-adipocytes with Western blotting. Knock-down of the thyroid hormone receptor α1 (TRα1) in 3T3-L1 cells was achieved with an appropriate silencing RNA (siRNA). KEY RESULTS: Single injections of T3 (7 ng·g⁻¹ i.p.) rapidly and markedly attenuated hyperglycemia. Treatment with T3 (14 ng·g⁻¹·day⁻¹, 18 days) dose-dependently attenuated blood glucose and increased insulin sensitivity in db/db mice. Higher doses of T3 (28 ng·g⁻¹·day⁻¹) reversed insulin resistance in db/db mice. T3 also increased insulin levels in plasma and the neurogenic differentiation factor (an insulin synthesis transcription factor) and insulin storage in pancreatic islets in db/db mice. These anti-diabetic effects of T3 were abolished by the PI3-kinase inhibitor (LY294002). In 3T3-L1 preadipocytes, T3 enhanced insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and activation of PI3-kinase, effects blocked by siRNA for TRα1. CONCLUSIONS AND IMPLICATIONS: T3 potentiated insulin signaling, improved insulin sensitivity, and increased insulin synthesis, which may contribute to its anti-diabetic effects. These findings may provide new approaches to the treatment of type 2 diabetes. |
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Authors:
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Yi Lin; Zhongjie Sun |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: British journal of pharmacology Volume: 162 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-13 Completed Date: 2011-07-26 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 597-610 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adipocytes / drug effects, metabolism Animals Basic Helix-Loop-Helix Transcription Factors / genetics, metabolism Blood Glucose / metabolism Blood Pressure Determination Body Temperature / drug effects Body Weight / drug effects Diabetes Mellitus, Type 2 / drug therapy*, metabolism Disease Models, Animal Heart Rate / drug effects Hyperglycemia / drug therapy*, metabolism Hypoglycemic Agents / pharmacology* Insulin / blood, metabolism*, pharmacology Insulin Resistance* Islets of Langerhans / drug effects, metabolism Male Mice Mice, Mutant Strains Nerve Tissue Proteins / genetics, metabolism Phosphatidylinositol 3-Kinases / metabolism Signal Transduction / drug effects* Triiodothyronine / metabolism, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL-077490/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Basic Helix-Loop-Helix Transcription Factors; 0/Blood Glucose; 0/Hypoglycemic Agents; 0/Insulin; 0/Nerve Tissue Proteins; 169238-82-8/NeuroD protein; 6893-02-3/Triiodothyronine; EC 2.7.1.-/Phosphatidylinositol 3-Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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