Decreased Insulin Binding to Lymphocytes from Diabetic Subjects

Unlabelled: We have studied insulin binding to circulating lymphocytes isolated from 20 untreated adult, nonobese, nonketotic, diabetic subjects with fasting hyperglycemia, 20 normal subjects, and four patients with fasting hyperglycemia secondary to chronic pancreatitis. The results of these studies show that lymphocytes from diabetic patients have decreased ability to specificity bind insulin when compared to lymphocytes from normal subjects. For example, when lymphocytes from diabetic patients and a trace amount of [(125)I]insulin (3.3 x 10(-11) M) were incubated, binding was less than 50% of the value obtained with lymphocytes from normal subjects (2+/-0.2% vs. 4.2+/-0.4%). Furthermore, the data show that lymphocytes from diabetic patients have only 1,200 insulin receptor sites per cell compared to 2,200 sites per cell for lymphocytes from normal subjects. Competitive inhibition studies using unlabeled insulin indicate that the affinity for insulin of lymphocytes from both groups is comparable. Consequently the decreased insulin binding of diabetics' lymphocytes is primarily due to a decreased number of available receptors rather than decreased binding affinity. This decreased insulin binding is not due to chronic hyperglycemia since insulin binding to lymphocytes, obtained from four patients with fasting hyperglycemia secondary to chronic pancreatitis, was completely normal. The possibility that some factor present in the plasma of diabetic patients could cause decreased insulin binding also seems unlikely since we could demonstrate no in vitro effects of diabetics' plasma on insulin binding. Lastly, the proportion of lymphocytes which were thymus derived and bone marrow derived were the same in each of the study groups indicating that differences in lymphocyte subpopulations do not account for our results.

In Conclusion: (a) lymphocytes from nonobese, untreated, adult diabetic patients with fasting hyperglycemia demonstrate a decreased ability to bind insulin; (b) this decreased insulin binding to lymphocytes obtained from diabetic patients can be accounted for primarily by an absolute decrease in the number of available receptor sites per cell; and (c) these data suggest that this defect in insulin binding is a primary phenomenon.