Exercise-induced regulation of insulin receptor affinity: role of circulating metabolites

We have described before that different forms of physical exercise induce bidirectional changes of insulin binding of monocytes (Michel G., Vocke T., Fiehn W., Weicker H., Schwarz W., Bieger W.P.: Am J Physiol 246: E 156-E 159, 1984). In vitro experiments suggested these changes to be due to dialyzable serum components. In this study, we investigated several hormones and metabolites as to their capacity to alter insulin binding in vitro. Somatostatin (100 pg/ml) and prostaglandin B1 (10 nmol/l) were the only hormonal agents producing a small and reversible (somatostatin) increase in monocyte insulin binding. Ketones were only effective at concentrations unphysiologically high. Acidosis diminished insulin binding to monocytes to about 35% of that found at pH 7.6. Lactate (10 mmol/l) induced a 28% drop in cellular insulin binding at low pH. The effect persisted after removal of the agent and may hence account for some of the decrease in cellular insulin binding observed after exhaustive exercise. Although the effect of acidosis was reversible in vitro, it may add considerably to the effect of lactate under in vivo conditions. The dialyzable serum factors responsible for the enhancement of binding affinity after long-term moderate exertion remain unknown. Free fatty acids proved effective in increasing monocyte insulin binding (14% with 1 mmol/l oleic acid) in vitro.