Insulin binding to isolated circulating monocytes from normal subjects and adult patients with diabetes was studied. The diabetic subjects were nonketotic, and their degree of glucose intolerance varied from an abnormal oral glucose tolerance test (chemical diabetes) to significant fasting hyperglycemia. The results indicated that patients with chemical diabetes had a 45 per cent decrease in insulin binding to monocytes, and this decrease was secondary to a reduction in the number of receptor sites per cell (normals, 15,000 sites per monocyte versus 8,500 sites per mono-cyte for chemical diabetics). When the individual data from the normal and chemical diabetic subjects were examined, a highly significant inverse correlation was found between the amount of insulin bound and both the fasting plasma insulin level (r = 0.61, P > 0.001) and the incremental insulin area during an oral glucose tolerance test (r = 0.49, P > 0.001). Furthermore, insulin binding was closely and inversely correlated to the degree of insulin resistance (r = 0.65, P > 0.001) among these subjects. Thus, the ability to bind insulin is inversely related to both the plasma insulin level and insulin sensitivity, and chemical diabetics who are insulin-resistant and hyperinsulinemic have a decreased ability to bind insulin. Many patients with fasting hyperglycemia also have decreased insulin binding. However, although as a group these pa tients have fasting hyperinsulinemia, they are hypoinsulinemic in response to a glucose challenge. Thus, inclusion of their data with that of the normal and chemical-diabetic patients enhances the relationship between insulin binding and fasting insulin level (r = 0.68, P > 0.001) but obliterates the relationship between insulin binding and incremental insulin area. Furthermore, in these subjects no significant correlation was found between insulin binding and the degree of insulin resistance (r = 0.19, N.S.), suggesting that all or most of the insulin resistance in these subjects was independent of changes in insulin receptors. In conclusion, (1) if the subjects are taken as a group, in patients with chemical diabetes and in diabetic patients with fasting hyperglycemia, insulin binding to monocytes is decreased; (2) over the entire spectrum of adult, nonketotic diabetes, insulin binding is decreased to monocytes from patients with fasting hyperinsulinemia, while subjects with normal insulin levels have normal insulin binding; (3) the insulin resistance of patients with chemical diabetes may be related to a decrease in insulin receptors, but this does not appear to be the case for patients with fasting hyperglycemia; and (4) plasma insulin levels are inversely related to insulin binding, but it is the basal, not the stimulated levels that are associated with changes in insulin receptors.
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Original Contributions| July 01 1977
Insulin Binding in Diabetes: Relationships with Plasma Insulin Levels and Insulin Sensitivity
Jerrold M Olefsky, MD;
Jerrold M Olefsky, Gerald M Reaven; Insulin Binding in Diabetes: Relationships with Plasma Insulin Levels and Insulin Sensitivity. Diabetes 1 July 1977; 26 (7): 680–688. https://doi.org/10.2337/diab.26.7.680
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