Independent stimulation of glucose metabolism and Na+-K+ exchange by insulin in the human forearm

Abstract

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)

Vascular function, insulin resistance and fatty acids

“…In the same study [19], prevention of insulin-mediated vasodilation by direct intra-arterial infusion of an inhibitor of nitric oxide synthase, L-NMMA, reduced glucose uptake by about 35% indicating that changes in blood flow modulate glucose uptake. Using different vasoconstrictor drugs such as angiotensin II [20], norepinephrine [21], or ouabain [22], similar reductions in insulin-mediated glucose uptake have been shown supporting the notion that changes in blood flow can modulate insulinmediated glucose uptake. On the other hand, data from studies evaluating the effect of pharmacologically-increased blood flow on insulin-mediated glucose uptake are less clear.…”

Dynamics of blood electrolytes in repeated hyper- and/or hypoglycaemic events in patients with type 1 diabetes

“…Insulin plays an important part in ionic regulation by its stimulatory effect [11][12][13] on the Na + /K + pump. The increase in the K + levels during hyperglycaemia in protocol 1 may thus be explained by the withdrawal of that insulin, which was given to keep the study participants euglycaemic at baseline.…”

“…Experimental work on many different tissues in vitro has shown that insulin has a stimulating effect on the Na + /K + pump [8][9][10]. In vivo, in studies in humans, this stimulatory effect on the Na + /K + pump is active at baseline insulin levels [11], and has been shown to be the cause of insulin-induced decreases in plasma K + after local perfusion of the forearm with insulin [12,13]. The stimulatory effect of insulin on the Na + /K + pump is also widely believed to underlie the hypoglycaemia-induced hypokalaemia [6,7].…”

The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers

“…Alternatively, insulin may act via direct modulation of transmembrane cation exchange mechanisms. Thus, insulin has been shown to stimulate Na+/K+ATPase and the Na+/K+pump in a variety of tissues, including vascular smooth muscle [42][43][44]. Stimulation of the Na+/K+pump induces hyperpolarisation and thereby decreases calcium influx via voltage-operated channels [45].…”