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Br J Pharmacol. 2011 Feb;162(3):597-610. doi: 10.1111/j.1476-5381.2010.01056.x.

Thyroid hormone potentiates insulin signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes.

Author information

1
Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Abstract

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.

PMID:
20883475
PMCID:
PMC3041250
DOI:
10.1111/j.1476-5381.2010.01056.x
[Indexed for MEDLINE]
Free PMC Article

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