1. ペプチドルホルモンのレセプター (インスリンを中心として)

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Insulin is secreted from pancreatic B-cells, acts on liver cells, and is distributed throughout the target cells of the body. When it acts on the target cells, it must bind to the specific receptor on the surface of the cell membrane.<BR>In this paper I reported on the binding characteristics of insulin on adipocytes of rats and pigs, the changes in insulin action in various pathological conditions, and finally some properties of anti-insulin receptor antibodies on adipocyte metabolism. The changes in the number of insulin receptor sites are closely associated with the circulating insulin concentration. When rats were fasted for 24 hr., the binding of insulin to the adipocytes increased mainly due to the increase in receptor number and not to the change in affinity, and these changes were restored by refeeding. These changes of the binding were reversely correlated with the change in plasma IRI concentrations. 2-deoxyglucose uptake and the glucose oxidation by the adipocytes were also decreased by fasting; however the latter was more pronouncedly disordered. When expressed as a percent change above basal, adipocytes obtained from fasted and control rats revealed similar insulin effects on glucose transport per unit insulin bound to the cells, suggesting that the coupling mechanism between receptor and effector was not significantly disturbed. However when the values were expressed in absolute terms, basal and insulin-stimulated glucose transport was significantly lower with fasting. Similar increase in number and not in affinity, of insulin receptors of adipocytes was demonstrated in streptozotocin treated diabetic rats. Plasma IRI levels were significantly lower in diabetic than in control rats.<BR>In a clinical study, we investigated the insulin binding to the peripheral circulating mononuclear cells obtained from several pathological conditions. The specific binding of insulin to the cells was lower in lipoatrophic diabetes, Werner syndrome, and in extreme obese states; however, the binding was not significantly different between hyperglycemic diabetics (FBS>140) and normal controls.<BR>There are several factors which are known to compete with insulin on binding with insulin receptors : they are NSILAs, somatomedin A and anti-insulin receptor antibodies. Plasma gamma globulin fraction obtained from a Sjögren syndrome with extreme insulin resistance revealed insulin-like activities on rat as well as on human adipocytes. They were the promotion of glucose transport, glucose oxidation and protein synthesis, and the inhibition of lipolysis. When the antibody was present in the incubation medium, the binding of insulin to the adipocytes was suppressed by the reduction in affinity. The discrepancy between the insulin action in vivo and in vitro are not disclosed on this pathological condition. The possibilities of the specific changes in the receptor of the patient's own cells were discussed.
日本内分泌学会の論文

1. ペプチドルホルモンのレセプター (インスリンを中心として)

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