Hypoglycaemia: glucose counterregulation, cardiovascular responses and immunoregulation

Maintenance of the plasma glucose concentration is crucial to survival of the brain and, therefore, the organism. Rapidly induced hypoglycaemia elicits an array of neuroendocrine responses that includes increased secretion of pancreatic glucagon and adrenomedullary epinephrine [ I , 21. Recent studies in humans indicate that glucagon plays a primary role in promoting glucose recovery, that epinephrine compensates largely for deficient glucagon secretion and that recovery from hypoglycaemia fails to occur only in the absence of both glucagon and epinephrine secretion [3-51. To the extent that they have deficient glucagon secretory responses, as they commonly do [6], patients with insulin dependent diabetes mellitus are dependent upon epinephrine to promote recovery from hypoglycaemia [7]. I f deficient epinephrine secretory responses develop as the result ofdiabetic adrenergic neuropathy [8]. such patients become defenceless against hypoglycaemia [9]. Glucagon acts primarily. perhaps exclusively, on the liver to increase glucose production under physiologic conditions. The mechanisms by which epinephrine raises the plasma glucose concentration are more complex. They involve both direct and indirect actions and are mediated through both aand Y-adrenergic receptors [ 10-12]. Alpha-adrenergic limitation of insulin secretion is an important indirect hyperglycaemic action of epinephrine. Beta-adrenergic stimulation of glucagon secretion also occurs (131 although its contribution to the hyperglycaemic response has been questioned [14]. Epinephrine acts directly to increase hepatic glucose production, an effect mediated predominantly, but not exclusively, through 8-adrenergic mechanisms in humans. In addition, it limits glucose utilization, also through 8-adrenergic mechanisms. Epinephrine induced increments in hepatic glucose production, like those produced by glucagon, are transient over about 90 min although both hormones continue to support glucose production at basal rates. In contrast, epinephrine induced limitation of glucose utilization is persistent. Thus, epinephrine induced increments in plasma glucose are sustained whereas glucagon induced increments are transient. The neuroendocrine responses to hypoglycaemia also result in a variety of physiologic changes unrelated to glucoregulation. Tachycardia, resulting in part from sympathoadrenal activation, is well recognized. Other haemodynamic effects are partially masked by the