Role of insulin and glucose in the induction of hypoaminoacidemia in man: studies in normal, juvenile diabetic, and insuloma patients

Abstract

It is generally assumed, but not established, that the lowering of plasma free amino acid levels following glucose intake is entirely mediated by stimulated insulin secretion. This problem was investigated in groups of healthy volunteer subjects, juvenile diabetics, and insuloma patients. The plasma concentrations of 15 individual free amino acids, glucose, and insulin or C-peptide were determined before and at intervals after either oral glucose (75 Gm.) or intravenous glucose (0.25 Gm. per kilogram of body weight) or tolbutamide (1 Gm.). Glucose lowered plasma amino acid levels in both situations of stimulated (healthy volunteer subjects) and absent (diabetic) insulin secretion. The lack of insulin response in juvenile diabetics was evident by the lack of any significant increase in C-peptide levels following glucose ingestion. Nevertheless, despite markedly greater plasma glucose levels, hypoaminoacidemia was less severe in diabetics than in normal volunteer subjects. In comparison to healthy volunteer subjects who showed significant decreases in concentrations of 14 of 15 examined amino acids by glucose, the diabetic individuals exhibited significant decreases in concentration of 8 amino acids (leucine, isoleucine, valine, tyrosine, phenylalanine, methionine, citrulline, and arginine). In face of a massively greater insulin response in an insuloma patient (greater than 1,000 muU per milliliter), the decreases in the levels of individual free amino acids following glucose were within the range of values obtained in the normal volunteer subjects. The stimulation of insulin secretion with tolbutamide also lowered the concentrations of free amino acids in plasma. However, one importnat difference distinguished the effect of tolbutamide from that of glucose. Within a few minutes after the injection of tolbutamide, there was a marked and persistent fall in alanine levels, while during the entire course of the glucose tolerance test there were no significant changes in the level of this amino acid, suggesting a difference in the mechanism of hypoaminoacidemia induced by endogenous insulin in the presence or absence of exogenous glucose. Despite a markedly greater insulin response to tolbutamide in the insuloma patient (greater than 1,500 muU per milliliter), the decreases in plasma glucose and free amino acid levels fell within the range of values obtained in normal volunteer subjects. In conclusion, the exogenous glucose per se lowers the levels of free amino acids in plasma. This effect is enhanced by insulin.