Muscle-specific Pten deletion protects against insulin resistance and diabetes

N Wijesekara, D Konrad, M Eweida… - … and cellular biology, 2005 - Taylor & Francis
N Wijesekara, D Konrad, M Eweida, C Jefferies, N Liadis, A Giacca, M Crackower, A Suzuki
Molecular and cellular biology, 2005Taylor & Francis
Pten (phosphatase with tensin homology), a dual-specificity phosphatase, is a negative
regulator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Pten regulates a
vast array of biological functions including growth, metabolism, and longevity. Although the
PI3K/Akt pathway is a key determinant of the insulin-dependent increase in glucose uptake
into muscle and adipose cells, the contribution of this pathway in muscle to whole-body
glucose homeostasis is unclear. Here we show that muscle-specific deletion of Pten …
Pten (phosphatase with tensin homology), a dual-specificity phosphatase, is a negative regulator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Pten regulates a vast array of biological functions including growth, metabolism, and longevity. Although the PI3K/Akt pathway is a key determinant of the insulin-dependent increase in glucose uptake into muscle and adipose cells, the contribution of this pathway in muscle to whole-body glucose homeostasis is unclear. Here we show that muscle-specific deletion of Pten protected mice from insulin resistance and diabetes caused by high-fat feeding. Deletion of muscle Pten resulted in enhanced insulin-stimulated 2-deoxyglucose uptake and Akt phosphorylation in soleus but, surprisingly, not in extensor digitorum longus muscle compared to littermate controls upon high-fat feeding, and these mice were spared from developing hyperinsulinemia and islet hyperplasia. Muscle Pten may be a potential target for treatment or prevention of insulin resistance and diabetes.
Taylor & Francis Online