The relation between insulin and adipocyte insulin receptors during treatment of human obesity

Seventeen obese patients were submitted to 1 week's severe then 3 months moderate dietary restriction. The glycaemic and insulinaemic response to oral glucose was measured at baseline, after 1 week and at 3 months, and the results related to adipocyte insulin receptors estimated from fat biopsies taken on each occasion and to the weight lost. Adipocyte insulin binding was found to be significantly inversely correlated with the insulinaemic response to oral glucose (r = -0.54, P less than 0.05), an inverse relationship maintained even after weight loss had been achieved and displayed within as well as between subjects. Variation of 125I-insulin binding to adipocytes was related to receptor number and not to receptor affinity and could not be accounted for by differences in 125I-insulin degradation. Adipose cell size did not correlate significantly either with the insulinaemic response or with cell surface receptor density. The findings suggest: (1) that a significant proportion of obese subjects are not hyperinsulinaemic and that their metabolic response to weight reduction may differ from that of those who are hyperinsulinaemic; (2) that reduced insulin binding to adipocytes in the obese reflects hyperinsulinaemia, when present, and not adiposity as such; (3) that the degree of insulinaemia is a major determinant of the cell surface receptor density.