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J Appl Physiol (June 27, 2003). doi:10.1152/japplphysiol.00199.2003
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Submitted on February 26, 2003
Accepted on June 23, 2003

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

Michael J Christopher1*, Zhi-Ping Chen2, Christian Rantzau1, Bruce E Kemp2, and Frank P Alford1

1 Department of Endocrinology & Diabetes, St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
2 St Vincent's Institute of Medical Research, University of Melbourne, Melbourne, Victoria, Australia

* To whom correspondence should be addressed. E-mail: christm{at}svhm.org.au.

The effect of diabetes and exercise on skeletal muscle (SkM) AMP-activated protein kinase (AMPK) {alpha}1 and {alpha}2 activities and site-specific phosphorylation of acetyl CoA carboxylase (ACC{beta}) was examined in the same six dogs before alloxan (35 mg/kg)-induced diabetes (C), and after 4-5 weeks 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 (VO2 max)) to measure the rate of glucose disposal into peripheral tissues (Rdtissue). SkM biopsies were taken from the thigh (vastus lateralis) before and immediately following exercise. In the C and DHG states, the rise in plasma free fatty acids (FFA) with exercise (~40%) was similar. In the DNG group, pre-exercise FFA were significantly higher, but the rise in absolute FFA with exercise was similar. However, the exercise-induced increment in Rdtissue was significantly blunted (by ~40-50%) in the DNG group compared with the other states. In SkM, pre-exercise AMPK{alpha}1 and {alpha}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, pre-exercise ACC{beta} phosphorylation in both diabetic states were elevated by ~70-80%, but the increases with exercise were similar to the C group. Pre-exercise AMPK{alpha}1 and {alpha}2 activities were negatively correlated with Rdtissue during exercise for the combined groups (both P < 0.02). In conclusion, the elevated pre-exercise SkM AMPK{alpha}1 and {alpha}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.




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