A New view of Insulin Action

Abstract

Insulin not only stimulates the Na-K-pump,but by stimulating the Na:H exchange pump increases intracellular pH, pHi. Fidelman et al (1982) found, as predicted by thermodynamic theory, the effect of insulin on glycolysis varied linearly with log[Na]o with the insulin effect being converted from stimulation of glycolysis to a 51% inhibition at 0.12 mM Nao.Zierler & Rabinowitz (1964) demonstrated in the forearm of human males that levels of insulin too low to affect glucose uptake, as little as 38 micro units per ml, was sufficient to stimulate the Na-K-pump, as reflected by increased potassium uptake, while producing no effect upon glucose uptake. This one experiment forces us to realize that the main action of insulin is not to regulate blood glucose levels, but to regulate the Na-K-pump and Na:H exchange. Since the Na-K-pump uses about 25% of the ATP production in a resting muscle, stimulation of the Na-K-pump increases the consumption of ATP so much that at high levels of stimulation, it is necessary to get more glucose into the cell to manufacture more ATP.Since insulin decreases Nai, elevates pHi, and increases production of ATP, one would expedt that the decreased insulin, such as seen in diabetes or in fasting would result in the reverse of these changes. Lowering plasma levels of insulin in rats by small doses of streptozotocin or by fasting produced an increase in Nai of about 30%, a decrease in pHi of 0.15 units, and a 24% decrease in ATPi.The action of thiazide diuretics to cause type 2 diuretics has been shown to be due to their ability to cause potassium loss. Not surprisingly, diets with large amounts of potassium and small amounts of sodium have been shown to reverse diabetes.