Fluctuations in the affinity and concentration of insulin receptors on circulating monocytes of obese patients: effects of starvation, refeeding, and dieting.
Open Access
- 1 November 1976
- journal article
- research article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 58 (5) , 1123-1135
- https://doi.org/10.1172/jci108565
Abstract
The binding of 125I-insulin to insulin receptors on circulating monocytes of obese patients and normal volunteers has been determined under various dietary states. In the basal, fed state the monocytes of obese patients with clinical insulin resistance (n= 6) bound less insulin than normals (n =10) because of a decrease in insulin receptor concentration (obese = 6,000-13,000 sites per monocyte versus normals 15,000-28,000 sites per monocyte). The single obese patient without evidence of clinical insulin resistance demonstrated normal binding of insulin with 16,000 sites per monocyte. In all patients, the total receptor concentration was inversely related to the circulating levels of insulin measured at rest after an overnight fast. For the obese patients with basally depressed insulin binding, a 48-72-h fast lowered circulating insulin and increased binding to normal levels but only at low hormone concentrations; this limited normalization of 125I-insulin binding was associated with increased receptor affinity for insulin without change in receptor concentration. Refeeding after the acute fasting periods resulted in return to the elevated plasma insulin levels, the basal receptor affinity, and the depressed insulin binding observed in the basal, fed state. Chronic diet restored plasma insulin levels, insulin binding, and receptor concentration to normal without change in affinity. When the data from this study are coupled with previous in vivo and in vitro findings they suggest that the insulin receptor of human monocytes is more sensitive to regulation by ambient insulin than the receptors of obese mice and cultured human lymphocytes. The results further indicate than an insulin receptor undergoes in vivo modulation of its interaction with insulin by changing receptor concentration and by altering the affinity of existing receptors.This publication has 29 references indexed in Scilit:
- Cooperativity in ligand binding: A new graphic analysisBiochemical and Biophysical Research Communications, 1975
- Insulin Receptor Deficiency in Genetic and Acquired ObesityJournal of Clinical Investigation, 1975
- Insulin Receptors in the Heart Muscle: Demonstration of Specific Binding Sites and Impairment of Insulin Binding in the Plasma Membrane of the Obese Hyperglycemic MouseDiabetes, 1975
- Insulin binding to liver plasm membranes in the obese hyperglycemic (ob/ob) mouse. Demonstration of a decreased number of functionally normal receptors.Journal of Biological Chemistry, 1975
- Insulin Receptor: Role in the Resistance of Human Obesity to InsulinScience, 1975
- Protein interactions with small molecules. Relationships between stoichiometric binding constants, site binding constants, and empirical binding parameters.Journal of Biological Chemistry, 1975
- Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparations of humah peripheral blood mononuclear leukocytes: implications for studies of insulin-resistant states in man.Proceedings of the National Academy of Sciences, 1975
- Defect in insulin binding to receptors in obese man. Amelioration with calorie restriction.Journal of Clinical Investigation, 1975
- Preparation of Iodine-131 Labelled Human Growth Hormone of High Specific ActivityNature, 1962
- IMMUNOASSAY OF ENDOGENOUS PLASMA INSULIN IN MANJournal of Clinical Investigation, 1960