title: Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise.
abstract: The effect of diabetes and exercise on skeletal muscle (SkM) AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activities and site-specific phosphorylation of acetyl-CoA carboxylase was examined in the same six dogs before alloxan (35 mg/kg)-induced diabetes (C) and after 4-5 wk of suboptimally controlled hyperglycemic and hypoinsulinemic diabetes (DHG) in the presence and absence of 300-min phlorizin (50 microg.kg-1.min-1)-induced "normoglycemia" (DNG). In each study, the dog underwent a 150-min [3-3H]glucose infusion period, followed by a 30-min treadmill exercise test (60-70% maximal oxygen capacity) to measure the rate of glucose disposal into peripheral tissues (Rdtissue). SkM biopsies were taken from the thigh (vastus lateralis) before and immediately after exercise. In the C and DHG states, the rise in plasma free fatty acids (FFA) with exercise ( approximately 40%) was similar. In the DNG group, preexercise FFA were significantly higher, but the absolute rise in FFA with exercise was similar. However, the exercise-induced increment in Rdtissue was significantly blunted (by approximately 40-50%) in the DNG group compared with the other states. In SkM, preexercise AMPKalpha1 and -alpha2 activities were significantly elevated (by approximately 60-125%) in both diabetic states, but unlike the C group these activities did not rise further with exercise. Additionally, preexercise acetyl-CoA carboxylase phosphorylation in both diabetic states was elevated by approximately 70-80%, but the increases with exercise were similar to the C group. Preexercise AMPKalpha1 and -alpha2 activities were negatively correlated with Rdtissue during exercise for the combined groups (both P < 0.02). In conclusion, the elevated preexercise SkM AMPKalpha1 and -alpha2 activities contribute to the ongoing basal supply of glucose and fatty acid metabolism in suboptimally controlled hypoinsulinemic diabetic dogs; but whether they also play a permissive role in the metabolic stress response to exercise remains uncertain.
authors.affiliation: Dept. of Endocrinology and Diabetes, St. Vincent's Hospital Melbourne, 35 Victoria Parade, Fitzroy 3065, Victoria, Australia. christm@svhm.org.au
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Christopher
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Christian
authors.initials: C
authors.lastname: Rantzau
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.forename: Frank P
authors.initials: FP
authors.lastname: Alford
mesh_terms: D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D004285:Dogs; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009043:Motor Activity; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D007527:Isoenzymes; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase