Affiliation:
1. Unité de Recherches de Diabétologie et d'Etudes Radio-Immunologiques des Hormones Protéiques, U.55 (Institut National de la Santé et de la Recherche Médicale), Hôpital Saint-Antoine 184 Rue du Faubourg Saint-Antoine, 7557 1 Paris Cedex 12, France
Abstract
The presence of insulin receptors in the heart muscle was investigated by measuring the binding of 125I-insulin to specific subcellular fractions of the rat and mouse myocardium. 125I-insulin bound to the plasma membrane fraction with a high degree of specificity and affinity. Insulin analogues competed with 125I-insulin in direct proportion to their biologic potency in vitro. Unlabeled insulin within the range of its concentrations in vivo inhibited 15 to 60 per cent of the 125I-insulin binding. The specific binding-sites were finite in number and represented about 90 per cent of the total binding. The insulin-binding capacity of the plasma membrane fraction was twelve- to fifteenfold higher than that of the mitochondrial fraction. As in the liver, the binding was time- and temperature-dependent with a slower but higher binding achieved at a lower temperature. The binding sites appeared to be heterogeneous with respect to affinity. At 5° C , the “higheraffinity” site had a K of about 2 × 109 M−1. No more than 10 percent of the 125I-insulin was degraded by the heart plasma membranes after one hour at 30° C. or twenty-two hours at 5° C.
Studies in the obese hyperglycemic (ob/ob) mouse revealed that the insulin binding is impaired in the heart muscle of this animal. Over a wide range of insulin concentrations, the plasma membrane fraction of ob/ob mice bound only 25 to 40 per cent as much insulin as did membranes of the thin littermates, suggesting that, as in the liver, the fat tissue, and the thymic lymphocyte, the number of insulin-binding sites is decreased in the heart of the ob/ob mouse. This defect selectively affected the plasma membrane fraction and could not be explained by differences in membrane purification or in insulin-degrading activity. Heart and liver membranes of fortyhour fasted ob/ob mice bound two to three times as much insulin as did membranes of ob/ob mice fed ad libitum.
These studies demonstrate and characterize the binding of insulin to heart muscle membranes; they extend to the heart muscle the insulin receptor defect also found in liver membranes and cells, in fat cell membranes, and in thymic lymphocytes of the ob/ob mouse.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
43 articles.
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