NA,K-ATPASE IN DIABETIC RAT SMALL-INTESTINE - CHANGES AT PROTEIN AND MESSENGER-RNA LEVELS AND ROLE OF GLUCAGON

Na,K-ATPase activity and isoform expression were measured in rat small intestinal mucosa taken from both normal and streptozocin-treated diabetic rats. Enzyme activity and abundance was 1.7-2.3-fold higher in rats diabetic for 2 wk than in controls. This was associated with 1.4-1.7-fold increases in small intestinal protein and DNA content. Ouabain inhibition curves of Na,K-ATPase were monophasic with K(i)s of 2.6 +/- 1.4 x 10(-4) and 2.0 +/- 1.2 x 10(-4) R I for control and diabetic rats, respectively (NS). Northern blot analysis revealed a 2.5-fold increase in mRNA(alpha 1) and a 3.4-fold increase in mRNA(beta 1) in diabetic rats relative to controls. Two thirds of this increase occurred within 24 h after injection of streptozocin. Immunoblots of intestinal enzyme preparations from diabetic and control rats indicated the presence of alpha 1 and beta 1 subunits but not of alpha 2 or alpha 3. Administration of glucagon (80 mu g/kg) to normal rats daily for 14-16 d increased mRNA alpha 1 3.1-fold but did not increase mRNA(beta 1) or enzyme activity. In experimental diabetes, alpha 1 and beta 1 isoforms of Na,K-ATPase are coordinately upregulated at both protein and mRNA levels, an effect which appears to be partially mediated by the associated hyperglucagonemia.