Exercise training decreases insulin resistance and increases glucose tolerance in conditions of prediabetes and overt Type 2 diabetes. However, the adaptive responses in skeletal muscle at the molecular and genetic level for these effects of exercise training have not been clearly established in an animal model of prediabetes. The present study identifies alterations in muscle gene expression that occur with exercise training in prediabetic, insulin-resistant obese Zucker rats and insulin-sensitive lean Zucker rats and are associated with a well-defined metabolic outcome. Treadmill running for up to 4 wk caused significant enhancements of glucose tolerance as assessed by the integrated area under the curve for glucose (AUCg) during an oral glucose tolerance test. Using microarray analysis, we identified a set of only 12 genes as both significantly altered by exercise training (>1.5-fold change; P < 0.05) and significantly correlated (P < 0.05) with the AUCg. Two genes, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and protein kinase C-ζ (PKC-ζ), are involved in the regulation of muscle glucose transport, and we provide the first evidence that PKC-ζ gene expression is enhanced by exercise training in insulin-resistant muscle. Protein expression of PGC-1α and PKC-ζ were positively correlated with the mRNA expression for these two genes. Overall, we have identified a limited number of genes in soleus muscle of lean and obese Zucker rats that are associated with both decreased insulin resistance and increased glucose tolerance following endurance exercise training. These findings could guide the development of pharmaceutical "exercise mimetics" in the treatment of insulin-resistant, prediabetic, or Type 2 diabetic individuals.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Jun 27 2007|
- Protein kinase c-ζ
- Skeletal muscle
ASJC Scopus subject areas