Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism

Diabetes. 2015 Dec;64(12):4023-32. doi: 10.2337/db14-1891. Epub 2015 Aug 25.

Abstract

Protein kinase C (PKC)δ 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 PKCδ in skeletal muscle in the control of insulin sensitivity and glucose metabolism by generating mice in which PKCδ was deleted specifically in muscle using Cre-lox recombination. Deletion of PKCδ 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 PKCδ did not rescue high-fat diet-induced insulin resistance or glucose intolerance. However, with an increase in age, PKCδ levels in muscle increased, and by 6 to 7 months of age, muscle-specific deletion of PKCδ 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-PKCδKO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKCδ in the regulation of mitochondrial mass at older age. These data indicate an important role of PKCδ in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity
  • Aging*
  • Animals
  • Blood Glucose / analysis
  • Diet, High-Fat / adverse effects
  • Energy Metabolism*
  • Enzyme Induction*
  • Enzyme Repression
  • Glucose Intolerance / blood
  • Glucose Intolerance / etiology
  • Glucose Intolerance / metabolism
  • Insulin / blood
  • Insulin Resistance*
  • Mice, Knockout
  • Mice, Transgenic
  • Mitochondria, Muscle / enzymology
  • Mitochondria, Muscle / metabolism*
  • Mitochondria, Muscle / pathology
  • Mitochondrial Dynamics
  • Muscle Development
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Obesity / blood
  • Obesity / etiology
  • Obesity / metabolism
  • Protein Kinase C-delta / genetics
  • Protein Kinase C-delta / metabolism*
  • Recombinant Proteins / metabolism

Substances

  • Blood Glucose
  • Insulin
  • Recombinant Proteins
  • Protein Kinase C-delta