Glucagon and Starvation

Abstract

When food supply is interrupted, survival is dependent upon a highly integrated metabolic response directed at maintaining glucose homeostasis and conserving body protein. Initially, the predominant metabolic requirement is the maintenance of a continuing supply of blood glucose for utilization by obligate glucose-consuming tissues, especially brain. Because liver glycogen stores are rapidly exhausted, continuing hepatic glucose production to maintain normoglycemia depends on an early acceleration of hepatic gluconeogenesis. However, since amino acids represent the sole precursors for de novo glucose synthesis, the demand for continuing glucose production imposes a steady drain on the body’s protein stores. Inasmuch as significant depletion of body protein (beyond 30%–50%) is generally fatal, survival during prolonged starvation ultimately depends upon a reduction of glucose consumption and a shift toward maximal utilization of fat, the body’s major storage fuel. The overall response to starvation may thus be characterized as biphasic, with the early, gluconeogenic phase most pronounced during the first 3–5 days, and the later, protein-conserving phase dominating after 2–4 weeks (Saudek and Felig 1976).