Glucagon and the Insulin:Glucagon Ratio in Diabetes and Other Catabolic Illnesses

Abstract

The biologic opposition which insulin and glucagon exert upon the liver and adipose tissue suggests that the relative concentrations of these two hormones which perfuse these tissues may determine their net nutrient balance. A review of recent studies of plasma glucagon and insulin levels reveals that the insulin:glucagon ratio (I/G) varies inversely with need for endogenous glucose production, being lowest in total starvation and highest during loading with exogenous carbohydrate. Similarly, the infusion of the glucose precursor, alanine, which in the fasting state causes a fall in I/G, a “catabolic response,” increases I/G during a glucose infusion, an ”anabolic response,/ which must spare alanine from gluconeogenesis. The same bihormonal relationship to need for glucose production has been observed after a protein load; normally after an overnight fast I/G rises in response to a beef meal, an anabolic response, while in the carbohydrate-deprived subject, the I/G does not rise, remaining at a catabolic level; during a glucose infusion the ingestion of a beef meal induces a greatly exaggerated anabolic rise in I/G. These findings are believed to account for certain previously poorly understood clinical observations. They may explain the so-called “protein sparing action” of glucose and the salutory nutritional effect of intravenously administered amino acid preparations when glucose is also provided in large quantities. The inability of diabetics to increase their I/G generally parallels their catabolic state, and, by stimulating glucagon but not insulin, tissue breakdown due to infection or trauma may further reduce the I/G and cause metabolic deterioration. The possible role of the I/G in the response to burns, trauma, infection, and malignancy is considered.