Glucoregulatory systems

Humans have two overlapping glucose-regulating systems that are activated by hypoglycemia: 1) the pancreatic α cells, which release glucagon, and 2) receptors in the hypothalamus, which respond to abnormally low concentrations of blood glucose. The hypothalamic glucoreceptors can trigger both the secretion of catecholamines (mediated by the sympathetic division of the autonomic nervous system) and release of adrenocorticotropic hormone (ACTH) and growth hormone by the anterior pituitary (Fig. 1). [Note: ACTH increases cortisol synthesis and secretion in the adrenal cortex .] Glucagon, the catecholamines, cortisol, and growth hormone are sometimes called the counterregulatory hormones because each opposes the action of insulin on glucose use.

Figure 1: A. Actions of some of the glucoregulatory hormones in response to low blood glucose. B. Glycemic thresholds for the various responses to hypoglycemia. [Note: Normal fasted blood glucose is 70−99 mg/dl.] + = weak stimulation; ++ = moderate stimulation; +++ = strong stimulation; 0 = no effect; ACTH = adrenocorticotropic hormone.

1. Glucagon and epinephrine: Secretion of these counterregulatory hormones is most important in the acute, short-term regulation of blood glucose levels. Glucagon stimulates hepatic glycogenolysis and gluconeogenesis. Epinephrine promotes glycogenolysis and lipolysis. It inhibits insulin secretion, thereby preventing GLUT-4–mediated uptake of glucose by muscle and adipose tissues. Epinephrine assumes a critical role in hypoglycemia when glucagon secretion is deficient, for example, in the late stages of type 1 diabetes mellitus . The prevention or correction of hypoglycemia fails when the secretion of both glucagon and epinephrine is deficient.
2. Cortisol and growth hormone: These counterregulatory hormones are less important in the short-term maintenance of blood glucose concentrations. They do, however, play a role in the long-term (transcriptional) management of glucose metabolism.