title: Exercise protects against diet-induced insulin resistance through downregulation of protein kinase Cβ in mice.
abstract: Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase Cβ (PKCβ) has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKCβ in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKCβ in exercise-attenuated insulin resistance in high-fat diet (HFD)-fed mice. PKCβ(-/-) and wild-type mice were fed a HFD with or without exercise training. PKC protein expression, body and tissue weight change, glucose and insulin tolerance, metabolic rate, mitochondria size and number, adipose inflammation, and AKT activation were determined to evaluate insulin sensitivity and metabolic changes after intervention. PKCβ expression decreased in both skeletal muscle and liver tissue after exercise. Exercise and PKCβ deficiency can alleviate HFD-induced insulin resistance, as evidenced by improved insulin tolerance. In addition, fat accumulation and mitochondrial dysfunction induced by HFD were also ameliorated by both exercise and PKCβ deficiency. On the other hand, exercise had little effect on PKCβ(-/-) mice. Further, our data indicated improved activation of AKT, the downstream signal molecule of insulin, in skeletal muscle and liver of exercised mice, whereas PKCβ deficiency blunted the difference between sedentary and exercised mice. These results suggest that downregulation of PKCβ contributes to exercise-induced improvement of insulin resistance in HFD-fed mice.
authors.affiliation: College of Public Health, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Rao
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Jixin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: College of Public Health, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.affiliation: College of Public Health, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Brianna
authors.initials: B
authors.lastname: Jordan
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Santosh
authors.initials: S
authors.lastname: Maurya
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Braunstein
authors.affiliation: College of Public Health, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Tse-Yao
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America ; Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America ; Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Sudha
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America ; Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Kamal
authors.initials: K
authors.lastname: Mehta
authors.affiliation: College of Public Health, The Ohio State University, Columbus, Ohio, United States of America ; Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D004032:Diet; D015536:Down-Regulation; D004435:Eating / Q000502:physiology; D015151:Immunoblotting; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal; D010805:Physical Conditioning, Animal / Q000502:physiology*; D064546:Protein Kinase C beta / Q000378:metabolism*
chemical_list: D064546:Protein Kinase C beta