Binding of 125I-insulin to the isolated glomeruli of rat kidney.
To investigate a possible action of insulin on the glomerulus, the binding 125I-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22 degrees C, 125I-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was less than 25% of total binding. A small fraction of 125I-insulin was degraded during incubation. This binding was specific to insulin in that it was inhibited by unlabeled porcine and beef insulins and to a lesser extent by porcine proinsulin and desalanine-desasparagine insulin, but not by glucagon, parathyroid hormone, vasopressin, calcitonin, and angiotensin II. Increasing concentrations of nonlabeled insulin displaced 125I-insulin binding in a dose-dependent fashion. Scatchard plot of the data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that demonstrate negative cooperativity. The addition of excess nonlabeled insulin to the glomeruli preincubated with 125I-insulin resulted in a rapid dissociation of approximately or equal to 70% of bound 125I-insulin. Insulin decreased the increments in glomerular cyclic AMP levels by epinephrine and by prostaglandin E2, but not those by histamine. These data showed the presence of specific insulin receptors in the glomeruli, and that insulin action may be, at least in part, through modulation of glomerular cyclic AMP concentrations. Such action of insulin may underlie the alteration in glomerular ultrafiltration and the glomerular ultrafiltration and the development of glomerular lesions in diabetes mellitus, a disease in which insulin deficiency or the tissue resistance to insulin exists.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology; D002417:Cattle; D003470:Culture Media; D046508:Culture Techniques; D005934:Glucagon / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D011384:Proinsulin / Q000494:pharmacology; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D013552:Swine
D003470:Culture Media; D006728:Hormones; D007328:Insulin; D007457:Iodine Radioisotopes; D010281:Parathyroid Hormone; D000804:Angiotensin II; D001127:Arginine Vasopressin; D002116:Calcitonin; D005934:Glucagon; D011384:Proinsulin; D011972:Receptor, Insulin