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Aim: Mitochondrial dysfunction has been suggested to play a significant role in obesity and insulin resistance. The aim of the present study was to investigate if changes in obesity and insulin resistance were related to similar changes in mitochondrial capacity for hydrogenperoxide release in Zucker diabetic fatty rats and their lean littermates. Methods: Thirty-four rats were used in this study. Rats were either lean or obese Zucker rats killed at 5-6 (young) or 12-14 (adults) weeks of age. Mitochondria were isolated from soleus muscles; respiration and release of hydrogenperoxide were determined and related to citrate synthase activity to determine intrinsic mitochondrial function. Mitochondrial-specific super-oxide dismuthase (MnSOD) protein content was determined in isolated mitochondria and muscle homogenate. Catalase protein content was determined in muscle homogenate. Results: Young lean and obese rats had a higher mitochondrial respiration when using palmitoyl- l-carnitine as substrate compared with adult lean and obese rats. The obese strain had higher mitochondrial hydrogenperoxide release but only in the adult animals. In both lean and obese animals, increased age was associated with increased mitochondrial hydrogenperoxide release. MnSOD tended to be higher in the obese strain in the isolated mitochondria. Regardless of age, catalase protein content was significantly lower in the obese rats. Conclusions: This study shows that the augmented increase in obesity and insulin resistance seen in Zucker diabetic fatty rats is associated with increased capacity for mitochondrial hydrogenperoxide release. [ABSTRACT FROM AUTHOR]

Aim: To investigate if exercise intensity and Ca2+ signalling regulate Na+,K+ pump mRNA expression in skeletal muscle. Methods: The importance of exercise intensity was evaluated by having trained and untrained humans perform intense intermittent and prolonged exercise. The importance of Ca2+ signalling was investigated by electrical stimulation of rat soleus and extensor digitorum longus (EDL) muscles in combination with studies of cell cultures. Results: Intermittent cycling exercise at ∼85% of VO2peak increased ( P < 0.05) α1 and β1 mRNA expression ∼2-fold in untrained and trained subjects. In trained subjects, intermittent exercise at ∼70% of VO2peak resulted in a less ( P < 0.05) pronounced increase (∼1.4-fold; P < 0.05) for α1 and no change in β1 mRNA. Prolonged low intensity exercise increased ( P < 0.05) mRNA expression of α1 ∼3.0-fold and α2 ∼1.8-fold in untrained but not in trained subjects. Electrical stimulation of rat soleus, but not EDL, muscle increased ( P < 0.05) α1 mRNA expression, but not when combined with KN62 and cyclosporin A incubation. Ionomycin incubation of cultured primary rat skeletal muscle cells increased ( P < 0.05) α1 and reduced ( P < 0.001) α2 mRNA expression and these responses were abolished ( P < 0.05) by co-incubation with cyclosporin A or KN62. Conclusion: (1) Exercise-induced increases in Na+,K+ pump α1 and β1 mRNA expression in trained subjects are more pronounced after high- than after moderate- and low-intensity exercise. (2) Both prolonged low and short-duration high-intensity exercise increase α1 mRNA expression in untrained subjects. (3) Ca2+i regulates α1 mRNA expression in oxidative muscles via Ca2+/calmodulin-dependent protein kinase (CaMK) and calcineurin signalling pathways. [ABSTRACT FROM AUTHOR]