Differential gene transcriptional regulation of G(i) isoforms and G(s) protein expression in diabetic rat hearts

Many cardiac diseases can be associated with alterations in the function an d quantity of G proteins. We examined the gene expressions and protein leve ls of G(i-1 alpha), G(i-2 alpha), G(i-3 alpha) and G(s alpha) in ventricula r myocardial preparations from rats 4-6 weeks after induction of diabetes w ith streptozotocin in comparison with those from age-matched control rats. Diabetic rat myocardium exhibited reductions in the protein levels of G(i-2 alpha) and G(i-3 alpha) by 22+/-2% and 57+/-2%, respectively. In diabetes, 22% and 53% reductions in myocardial mRNA levels of G(i-2 alpha) and G(i-3 alpha) were observed. Although a faint protein signal of G(i-3 alpha) was detectable, no apparent expression of mRNA for G(i-1 alpha) was found in ei ther control or diabetic myocardium. The reduced protein and mRNA levels of G(i-2 alpha) and G(i-3 alpha) were prevented by insulin therapy. No change was found in the protein and mRNA levels of G(s alpha) in diabetic myocard ium. In conclusion, diabetes leads to a differential regulation of protein expressions of G(i alpha) isoforms and G(s alpha) in ventricular myocardium . The reduced expression of G(i-2 alpha) and G(i-3 alpha), proteins can be explained, at least in part, by the decreases in the transcriptional levels .