Independent stimulation of glucose metabolism and Na+-K+ exchange by insulin in the human forearm.
Insulin promotes potassium uptake into skeletal muscle by stimulating the activity of the Na+-K+ pump. To test whether insulin-induced glucose and potassium uptake are linked processes in vivo, we used the perfused forearm technique in healthy volunteers. Local hyperinsulinemia (125 +/- 11 microU/ml for 100 min) induced a net uptake of glucose and potassium (4.79 +/- 0.61 and 0.76 +/- 0.22 mumol.min-1.100 ml-1 of forearm volume, respectively). When an intra-arterial ouabain infusion (0.72 microgram.min-1.100 ml-1, producing local levels of approximately 0.5 mM) was superimposed on the insulin infusion, potassium uptake was blocked (0.026 +/- 0.190 ml.min-1.100 ml-1, P less than 0.02), and glucose uptake was decreased (to 3.31 +/- 0.34 mumol.min-1.100 ml-1, P less than 0.03). The latter change was explained by a 30% fall in forearm blood flow (from 2.95 +/- 0.10 to 2.01 +/- 0.18 ml.min-1.100 ml-1, P less than 0.001). To separate out the effect of blood flow, in another series of studies forearm blood flow was clamped by co-infusing propranolol and phentolamine (7 and 8 micrograms.min-1.100 ml-1, respectively). Under these conditions of fixed flow (7.0 +/- 0.8 ml.min-1.100 ml-1), ouabain still abolished the stimulatory effect of insulin on potassium uptake but had only a small (and statistically insignificant) effect on forearm glucose extraction (from 20 +/- 2 to 16 +/- 2%, P = N>). We conclude that in human forearm muscle ouabain inhibits Na+-K+ exchange and depresses insulin-induced glucose uptake via an adrenergic-mediated limitation of blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferrannini
E
E
Metabolism Unit, Consiglio Nazionale delle Richerche Institute of Clinical Physiology, Pisa, Italy.
Taddei
S
S
Santoro
D
D
Natali
A
A
Boni
C
C
Del Chiaro
D
D
Buzzigoli
G
G
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005542:Forearm; D005947:Glucose / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D009132:Muscles / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose