title: Muscle-specific Pten deletion protects against insulin resistance and diabetes.
abstract: 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.
authors.affiliation: Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 2N9.
authors.forename: Nadeeja
authors.initials: N
authors.lastname: Wijesekara
authors.forename: Daniel
authors.initials: D
authors.lastname: Konrad
authors.forename: Mohamed
authors.initials: M
authors.lastname: Eweida
authors.forename: Craig
authors.initials: C
authors.lastname: Jefferies
authors.forename: Nicole
authors.initials: N
authors.lastname: Liadis
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
authors.forename: Mike
authors.initials: M
authors.lastname: Crackower
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Amira
authors.initials: A
authors.lastname: Klip
authors.forename: Minna
authors.initials: M
authors.lastname: Woo
mesh_terms: 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*
chemical_list: D007328:Insulin; D025521:Tumor Suppressor Proteins; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase