Small intestinal Na+,K+-adenosine triphosphatase activity and gene expression in experimental diabetes mellitus.

The Na+,K+-ATPase plays a key role in the absorption of electrolytes, water, and nutrients from the small intestine. The effect of streptozotocin-induced diabetes mellitus (STZ-DM) on the activity and expression of Na+,K+-ATPase in the rat small intestine was examined in the present study. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (75 mg/kg) and control and STZ-DM rats were killed at day 30 (chronic diabetic state). Levels of Na+,K+-ATPase activity and numbers of sodium pumps were increased two- to threefold in the jejunum and ileum. Sodium pump kinetics were unaltered in STZ-DM. The levels of Na+,K+-ATPase alpha1 and beta1 isoform protein, corresponding mRNAs, and levels of transcription were increased in the jejunal and ileal mucosa of the chronically diabetic rat. The increases in Na+,K+-ATPase functional activity, protein expression, and mRNA were most marked at the level of the ileal mucosa. While a proximal to distal gradient in Na+,K+-ATPase activity and subunit isoform protein levels were observed in both control and diabetic rats, levels of subunit isoform mRNA abundance were similar in both regions of the small intestine in both groups of rats. The alterations in small intestinal Na+,K+-ATPase expression in the chronic diabetic state appear to involve alterations in transcriptional and posttranscriptional events and may likely represent an adaptive response that leads to increased Na+-coupled monosaccharide absorption in the context of a perceived state of nutrient depletion.