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.
Choi
C S
CS
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9142, USA.
Thompson
C B
CB
Leong
P K
PK
McDonough
A A
AA
Youn
J H
JH
D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000378:metabolism*; D011191:Potassium Deficiency / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium