Summary
Insulin binding, insulin degradation and glucose metabolism were studied in highly purified preparations of monocytes. Steady state specific insulin binding was found at 15 °C, whereas no plateau was reached at 37 °C because of considerable insulin degradation at this temperature.125I-insulin nonspecifically bound to monocytes at 15 °C remained constant for 120 min. In contrast non-specifically bound125I-insulin increased during incubation at 37 °C. About one third dissociated slowly to a washout medium suggesting an intracellular uptake of this fraction of non-specifically monocyte bound insulin. Monocytes did not degrade insulin at 15 °C. At 37 °C insulin was degraded partly by “proteases” released from the cells and partly by the specific insulin receptor. We found that about 35% of the total monocyte receptor bound iodoinsulin dissociated to a washout medium as degraded insulin. Furthermore, the degradation velocity of receptor bound insulin was proportional to the receptor occupancy. Thus, at 37 °C receptor bound insulin is the substrate for insulin degradation in monocytes and the reaction between the insulin molecule and the insulin receptor is conceivably considered not to be bimolecular at 37 °C unlike at 15 °C. Previously, no biological effect of insulin on monocytes has been demonstrated. In this study we found that insulin increased glucose uptake (25%, p<0.01) and lactate release (12%, p<0.05) in monocytes with ED50-values within the physiological range. To obtain 50% of maximal biological effect it was necessary to activate only a few percent of the receptors.
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Beck-Nielsen, H., Pedersen, O. Insulin binding, insulin degradation and glucose metabolism in human monocytes. Diabetologia 17, 77–84 (1979). https://doi.org/10.1007/BF01222206
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DOI: https://doi.org/10.1007/BF01222206