Role of PKC? in Insulin Sensitivity and Skeletal Muscle Metabolism.

ABSTRACT: Protein kinase C (PKC)? has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKC? in skeletal muscle in the control of insulin sensitivity and glucose metabolism by generating mice in which PKC? was deleted specifically in muscle using Cre-lox recombination. Deletion of PKC? in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological levels of insulin. Likewise, in young mice, muscle-specific deletion of PKC? did not rescue high-fat diet-induced insulin resistance or glucose intolerance. However, with an increase in age, PKC? levels in muscle increased, and by 6 to 7 months of age, muscle-specific deletion of PKC? improved whole-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKC?KO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKC? in the regulation of mitochondrial mass at older age. These data indicate an important role of PKC? in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging.

SUBMITTER: Li M 

PROVIDER: S-EPMC4657586 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature