Acute and chronic effects of hyperglycaemia on glucose metabolism.
In normal man, several hormonal and metabolic adjustments allow the maintenance of the blood glucose concentration within narrow limits. Hyperglycaemia participates in this regulation via stimulation of glucose disposal and inhibition of glucose production. The effects are mediated, in addition to changes in insulin and glucagon secretion, by the mass-action effect of glucose. In both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients, hyperglycaemia, by mass-action abnormally elevates the basal glucose utilization rate but compensates for reduced postprandial insulin-stimulated glucose disposal. When exposed to chronic hyperglycaemia, the body tissues seem to protect themselves, at least partly, against excessive glucose utilization. These protective mechanisms include both a reduction in insulin stimulated glucose disposal and insulin secretion. Chronic hyperglycaemia may also reduce non-insulin-dependent glucose utilization, at least in rats. In Type 1 diabetic patients with normal peripheral insulin concentrations, chronic hyperglycaemia per se could be a major cause of insulin resistance. In Type 2 diabetic patients, insulin resistance is often already present before the development of overt fasting hyperglycaemia. At the diabetic stage, hyperglycaemia could, however, maintain a self-perpetuating cycle, where the deleterious effects of high glucose concentrations on insulin action and secretion cause further deterioration of glycaemic control. The biochemical basis for hyperglycaemia-induced insulin resistance is still far from clear, but could involve changes in the glucose transporter number and gene expression.
Yki-Järvinen
H
H
Second Department of Medicine, Helsinki University, Finland.
D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007333:Insulin Resistance
D005947:Glucose