Short-term K(+) deprivation provokes insulin resistance of cellular K(+) uptake revealed with the K(+) clamp.

We aimed to test the feasibility of quantifying insulin action on cellular K(+) uptake in vivo in the conscious rat by measuring the exogenous K(+) infusion rate needed to maintain constant plasma K(+) concentration ([K(+)]) during insulin infusion. In this "K(+) clamp" the K(+) infusion rate required to clamp plasma [K(+)] is a measure of insulin action to increase net plasma K(+) disappearance. K(+) infusion rate required to clamp plasma [K(+)] was insulin dose dependent. Renal K(+) excretion was not significantly affected by insulin at a physiological concentration ( approximately 90 microU/ml, P > 0.05), indicating that most of insulin-mediated plasma K(+) disappearance was due to K(+) uptake by extrarenal tissues. In rats deprived of K(+) for 2 days, plasma [K(+)] fell from 4.2 to 3.8 mM, insulin-mediated plasma glucose clearance was normal, but insulin-mediated plasma K(+) disappearance decreased to 20% of control, even though there was no change in muscle Na-K-ATPase activity or expression, which is believed to be the main K(+) uptake route. After 10 days K(+) deprivation, plasma [K(+)] fell to 2.9 mM, insulin-mediated K(+) disappearance decreased to 6% of control (glucose clearance normal), and there were 50% decreases in Na-K-ATPase activity and alpha2-subunit levels. In conclusion, the present study proves the feasibility of the K(+) clamp technique and demonstrates that short-term K(+) deprivation leads to a near complete insulin resistance of cellular K(+) uptake that precedes changes in muscle sodium pump expression.