Hormonal Control of Glucose Metabolism

Plasma glucose concentration is normally maintained within a narrow range despite wide fluctuations in the supply (meal) and demand (exercise) for nutrients. In adult humans, plasma glucose concentrations throughout a 24-hour period average 90 mg/ dl, with maximum values 60-90 minutes after meals, usually not exceeding 140 mg/ dl, and values during a moderate fast or exercise usually remaining above 50 mg/dl. This relative stability contrasts with the situation for other fuels such as glycerol, lactate, free fatty acids (FFA), and ketone bodies (acetoacetate and j3-hydroxybutyrate), the fluctuations of which vary more widely. The reason why plasma glucose concentration must be maintained in a narrow range of concentration is related to the deleterious effects of both hypoglycemia and hyperglycemia. Acute hypoglycemia is well known to have harmful effects on the brain. Glucose is usually the main fuel used by the brain; this is because plasma concentrations of one of the alternative fuels (ketone bodies) are low, while transport across the blood-brain barrier of the other alternative fuel (free fatty acids) is limited. As the brain has low energy stores, it is markedly dependent upon circulating glucose for its energy metabolism. When plasma glucose levels fall below 60 mg/dl, brain glucose uptake decreases and cerebral function is impaired. More severe and prolonged hypoglycemia can cause convulsions, permanent brain damage, and death. Chronic hyperglycemia also has deleterious effects. The functional and vascular changes in the eyes, nerves, aorta, and kidneys of diabetic patients seem to be related to increased metabolism of glucose via the polyol pathway. To maintain plasma glucose concentrations within a normal range, the changes in the dietary or endogenous glucose supply must be precisely matched by comparable changes in tissue uptake. Conversely, the changes in tissue glucose uptake (for example, during exercise) must be matched by appropriate changes in the exogenous or endogenous glucose supply.