Defects in insulin binding and autophosphorylation of erythrocyte insulin receptors in patients with syndromes of severe insulin resistance and their parents.

Genetic forms of severe insulin resistance are often characterized by alterations in binding and/or kinase properties of the insulin receptor. To evaluate whether alterations in insulin receptor kinase of erythrocytes can be used as genetic markers, we studied patients with two apparently inherited conditions of severe insulin resistance (leprechaunism and the type A syndrome of insulin resistance) and their families. In the two propositi, [125I]insulin binding to intact erythrocytes was decreased by 64% and 45%, respectively.

Role of muscle in CO2 production after oral glucose administration in man.

A significant increase in CO2 production, reflecting carbohydrate oxidation and/or fat synthesis, is observed in normal subjects after the ingestion of glucose. The anatomic site(s) of this CO2 production has not yet been localized, although liver and muscle are logical considerations. To assess the contribution of skeletal muscle to this process, we measured whole-body and forearm CO2 flux in normal, postabsorptive subjects after the ingestion of 100 g of glucose and calculated their total muscle CO2 production.

The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals.

We examined changes in spontaneously secreted growth hormone with aging by studying the 24-h integrated concentration of GH (IC-GH) of 173 nonobese subjects (height, greater than or equal to 5%; 7-65 yr of age). There was no significant difference in IC-GH on repeat testing of 13 men or in 23 women studied in the follicular and again in the luteal phase of the menstrual cycle. The level of IC-GH was strongly effected by age; children had the highest mean IC-GH, and there was a decline in IC-GH with increasing age after the second decade of life.

Hyperinsulinemia of obesity is due to decreased clearance of insulin.

The hyperinsulinemia of obesity could result from a decrease in the metabolic clearance rate of insulin (MCR-I), an increase in the secretory rate of insulin (SR-I), or a combination of both these processes. Because C-peptide and insulin are secreted in an equimolar ratio, the plasma concentrations of C-peptide (C) and insulin (I) are inversely proportional to their rates of metabolic clearance (C/I = MCR-I/MCR-C). We obtained 24-h integrated concentrations (IC) of insulin (IC-I) and C-peptide (IC-C) in 23 obese and 45 nonobese subjects over a period of normal activity and food intake.

Evidence for restoration of hepatic glucose processing in type I diabetes mellitus.

The role of muscle in the processing of dietary carbohydrate in nine type I diabetic patients was assessed using combined forearm-indirect calorimetry-glucose meal (100 g) studies performed before and after 72 h of artificial beta-cell directed insulin therapy. On conventional insulin therapy, initially elevated arterial glucose concentrations rose markedly, free insulin increased slightly, and the respiratory quotient (R.Q.