Muscle-specific Pten deletion protects against insulin resistance and diabetes.
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.
Wijesekara
Nadeeja
N
Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 2N9.
Konrad
Daniel
D
Eweida
Mohamed
M
Jefferies
Craig
C
Liadis
Nicole
N
Giacca
Adria
A
Crackower
Mike
M
Suzuki
Akira
A
Mak
Tak W
TW
Kahn
C Ronald
CR
Klip
Amira
A
Woo
Minna
M
D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D025521:Tumor Suppressor Proteins; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase