Adaptation of hepatic, renal, and intestinal gluconeogenesis during food deprivation

Abstract

The maintenance of plasma glucose is a vital necessity in all situations. Multiple adaptations permitting endogenous glucose production from the liver, kidneys, and gut take place during starvation. The mobilization of liver glycogen stores is the more rapid process to tune blood glucose from the moment where glucose availability from food starts to lack. Increased lipolysis from the adipose depots plays a crucial role to provide energy to the whole body and especially to allow the liver to carry out gluconeogenesis from lactate and alanine, which is an endergonic process. Proteolysis from skeletal muscles then supplies carbon skeletons to build glucose from amino acids released in blood. Among the exquisite late adaptations of gluconeogenesis taking place after the exhaustion of liver glycogen stores, the progressive replacement of hepatic gluconeogenesis by renal and intestinal gluconeogenesis (from glutamine) is essential, since it permits to maintain plasma glucose and in the same time to preserve energy balance of the body. Gluconeogenesis from glutamine, indeed, is an exergonic process. The late blunting in hepatic GNG paralleling the increase in intestinal GNG in late starvation allows the liver to store glycogen again, which might be a key adaptation for survival.