Protein metabolism in diabetes mellitus.

Insulin deficiency is a protein catabolic state. In vivo studies have shown that insulin enhances short-side-chain amino acid intracellular uptake, stimulates transcription and translation of RNA, increases the gene expression of albumin and other proteins and inhibits liver protein breakdown enzymes. In IDDM patients most of the whole-body protein turnover studies have shown that insulin deficiency increases protein breakdown and increases amino acid oxidation and that these effects are reversed by insulin treatment. Recent studies have demonstrated that a substantial increase in leucine transamination during insulin deprivation contributes to leucine catabolism in IDDM patients. Protein synthesis in the insulin-deprived state is also increased although to a lesser extent than protein breakdown, and this increased whole-body protein synthesis is reduced with an insulin infusion; thus the effects of insulin are largely mediated through its effects on protein breakdown. The metabolic derangements in diabetes frequently involve disturbances in substrates and hormones other than insulin. The observed effects of insulin deficiency in diabetic patients vary in different body compartments; most of the effects of insulin on protein synthesis appear to occur in non-muscular tissues especially in the splanchnic area. In addition, insulin has a differential effect on hepatic protein synthesis, i.e. inhibits fibrinogen synthesis and promotes albumin synthesis. Insulin's anticatabolic effect in IDDM patients is largely due to its inhibition of protein breakdown. The net protein anabolism due to insulin occurs largely in skeletal muscle. In patients with NIDDM these effects are not noted, presumably because of residual endogenous insulin secretion. In fact, treatments that result in improvement of glucose metabolism in obese NIDDM patients do not affect protein metabolism.