Glucagon and Glucose Counterregulation

Abstract

Glucose is the predominant metabolic fuel utilized by the brain (McCall 1993; Sokoloff 1989; Hasselbalch et al. 1994). Under physiological conditions glucose oxidation accounts for virtually all of the oxygen consumed by the brain, and the brain respiratory quotient approaches 1.0. The brain can utilize additional substrates, such as ketone bodies, but only when the circulating levels of these are elevated well above normal postabsorptive levels, as during prolonged fasting (Hasselbalch et al. 1994). Because the brain cannot synthesize glucose or store more than a few minutes’ supply as glycogen, it requires a continuous supply of glucose from the circulation for its survival and, therefore, for survival of the individual. At normal (or elevated) plasma glucose concentrations the rate of blood-to-brain glucose transport exceeds the rate of brain glucose metabolism. However, as the plasma glucose concentration falls below the physiological range blood-to-brain glucose transport becomes rate limiting to brain glucose metabolism. Given the survival value of maintenance of the plasma glucose concentration, it is not surprising that physiological mechanisms that very effectively prevent or correct hypoglycemia evolved.