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Thyroid hormone potentiates insulin
signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes
Author(s) -
Lin Yi,
Sun Zhongjie
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01056.x
Subject(s) - endocrinology , medicine , insulin , insulin receptor , insulin resistance , insulin receptor substrate , insulin oscillation , hormone , irs2 , chemistry , biology
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.