Abstract 13143: Exercise Protects against Diet-Induced Insulin Resistance Possibly via Down-Regulation of Protein Kinase C-Beta

Abstract

Introduction: It has been well-established that exercise can ameliorate high fat diet induced insulin resistance in both human and animal studies. However, the underlying mechanisms linking exercise and insulin sensitivity are poorly understood. Since isoforms of protein kinase C (PKC) are implicated in the pathogenesis of obesity and diabetes, we hypothesize that PKC-β is involved in regulating energy metabolism and insulin sensitivity by exercise.

Methods: Six-week-old male PKC-β-/- mice and C57BL/6 (WT) mice were fed a high fat diet (42% fat calorie) for 16 weeks. At the age of 14 weeks, both PKC-β-/- and WT mice were randomly assigned to sedentary (SED) or exercise (EX, trained on a treadmill at a speed of 15 m/min, for 40 min/day, 5 days/wk) group for 8 weeks. Body weights, intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were detected before and after exercise. Magnetic resonance imaging (MRI) was used to quantify fat depots at abdominal level. Oxymax Lab Animal Monitoring System (CLAMs) was used to assess both resting and exercise metabolic rate. Plasma insulin, leptin and adiponectin level were measured by ELISA.

Results: Exercise decreased body weight gain in both PKC-β-/- and WT mice (0.9 fold, p<0.05 EX vs. SED; n=8). Muscle weight in PKC-β-/- mice was higher than that in WT mice (0.32±0.029 vs. 0.28±0.015g, p=0.002 for EX PKC-β-/- vs. EX WT; 0.30±0.035 vs. 0.25±0.014g, p=0.006 for SED PKC-β-/- vs. SED WT; n=8) and exercise increased muscle weight in WT but not in PKC-β-/- mice (p=0.018 for EX WT vs. SED WT; n=8). In addition, fat pad weight was lower in PKC-β-/- mice (0.5 fold, p<0.05; n=8) but exercise had no significant effect. MRI showed similar results. Exercise improved IPGTT and ITT in WT mice, as well as insulin and leptin level (p<0.05; n=8). ITT, insulin and leptin level were lower in PKC-β-/- mice (p<0.05 vs. WT; n=8), but exercise showed no significant effect. CLAMs result showed PKC-β-/- mice had a better metabolic rate and exercise improved metabolic rate in WT but not in PKC-β-/- mice.

Conclusions: PKC-β may play an important role in regulating energy metabolism and insulin sensitivity by exercise.