Regulation of Na+,K(+)-ATPase gene expression by insulin in vascular smooth muscle cells

Na+,K(+)-ATPase gene expression and activity and its modulation by insulin were investigated in vascular smooth muscle cells (VSMC). Messenger RNAs encoding for alpha 1- and alpha 2-isoforms of Na+,K(+)-ATPase were identified in a pure population of cultured VSMC (a7r5 cells). The predominant isoform in VSMC was alpha 1, but only alpha 2 was regulated by insulin. Insulin treatment of VSMC for 1 and 6 h caused significant increases in mRNA encoding the alpha 2-subunit of Na+,K(+)-ATPase (n = 7, P < .01). Under similar conditions, insulin had no effect on alpha 1-Na+,K(+)-ATPase mRNA levels. VSMC treated with insulin exhibited a significant stimulation of ouabain inhibitable ATPase activity (1 h insulin, n = 3, v control, n = 3, P < .025; 6 h insulin, n = 3, v control, n = 3, P < .05). Changes in insulin regulation of Na+,K(+)-ATPase gene expression in vascular smooth muscle may be an important factor in the development of hypertension in diabetes.