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Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise

¹Department of Endocrinology and Diabetes, St. Vincent's Hospital Melbourne, Fitzroy 3065; ²Department of Medicine, University of Melbourne, Parkville 3052; and ³St. Vincent's Institute of Medical Research, Fitzroy 3065, Victoria, Australia

Submitted 26 February 2003 ; accepted in final form 23 June 2003

The effect of diabetes and exercise on skeletal muscle (SkM) AMP-activated protein kinase (AMPK)1 and -2 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 µg·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 (Rd_tissue). 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 (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 Rd_tissue was significantly blunted (by 40-50%) in the DNG group compared with the other states. In SkM, preexercise AMPK1 and -2 activities were significantly elevated (by 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 70-80%, but the increases with exercise were similar to the C group. Preexercise AMPK1 and -2 activities were negatively correlated with Rd_tissue during exercise for the combined groups (both P < 0.02). In conclusion, the elevated preexercise SkM AMPK1 and -2 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.

hyperglycemia; hypoinsulinemia; acetyl coenzyme A carboxylase; glucose and fatty acid metabolism; phlorizin-induced normoglycemia

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