The Effects of Acute and Chronic Starvation on Insulin Binding to Isolated Human Adipocytes*

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Abstract
The effects of acute and chronic starvation on insulin binding to isolated human adipocytes from obese subjects was studied. Three days of fasting led to a 38% increase in the ability of adipocytes to bind a tracer concentration of [125I]- insulin; this was due to enhanced receptor affinity with no change in receptor number. Fourteen days of fasting led to a greater increase (150%) in insulin binding due to a further rise in receptor affinity as well as an increase in receptor number to near normal levels. An increase in receptor affinity can be due to an increase in ka or a decrease in kd. In both acute and chronic starvation, the rates at which insulin dissociates from its receptors decreased (t½ = 32 ± 4, 46 ± 6, and 62 ± 5 min for the baseline period, 3-day fast, and 14-day fast, respectively), and the magnitude of these changes correlated quite well with the magnitude of the increase in receptor affinity. The dissociation of [125I]insulin was accelerated in the presence of a high concentration of unlabeled insulin (100 ng/ml) in the buffer, and the magnitude of this effect was the same in all experimental groups. In conclusion, 1) acute starvation leads to an increase in the ability of adipocytes to bind insulin due to an increase in receptor affinity, while chronic starvation leads to an increase in both receptor affinity and receptor number; 2) the increase in receptor affinity is due to a decrease in the insulin dissociation rate; 3) the increase in receptor number during the 14-day fast is most likely due to the chronic hyoinsulinemia; and 4) it is suggested that the short term adaptive response of the insulin receptor is a change in affinity, whereas the chronic response is a change in receptor number.

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