GlucagonAdrenaline and the sympathetic nervous systemCortisolGrowth hormone


As described in more detail here, the peptide hormone insulin is the primary control mechanism for metabolic adjustments and has the widest effect on a variety cells. It is secreted by the β-cells of the pancreas primarily in response to elevated glucose levels in blood. Insulin release is inhibited by sympathetic nerves innervating the pancreas and by circulating adrenalin. All the additional metabolic control systems described below can be categorised as glucose-counterregulatory control systems, that is, systems that oppose the actions of insulin by increasing blood glucose levels.


Glucagon is a peptide hormone that is released by α-cells of the endocrine pancreas in response to low blood glucose levels. Its effects on metabolism are not simply the opposite of those of insulin – in fact, they are more limited. Indeed, all of the important effects of glucagon take place in the liver: gluconeogenesis, glycogenolysis and ketone production (what does all this mean?). Glucagon secretion is also activated by sympathetic nerves to the pancreas and by circulating adrenaline. This fits with the general picture of the flight or fight response, where increased energy availability is required.

Circulating adrenaline and the sympathetic nervous system

Both sympathetic nerve-derived noradrenaline and adrenaline released by the adrenal gland have important effects on metabolism:

  • Pancreas: Sympathetic nerves/adrenaline increase glucagon secretion and inhibit insulin secretion.
  • Muscle: circulating adrenaline promotes gylcogenolysis
  • Liver: Either increase glycogenolysis and gluconeogenesis
  • Adipocytes: Either increase lipolysis


Cortisol is a steroid secreted by the adrenal cortex in response to stress, although it also has a background, diurnal pattern of secretion (highest in the late morning). People who have a cortisol deficiency (such as in adrenal insufficiency) develop sever hypoglycaemia when fasting, indicating that cortisol has an important role in controlling metabolism. However, cortisol secretion is not linked to the absorptive/post-absorptive states. Rather, cortisol secretion is required for the expression of liver and adipocyte enzymes required for gluconeogenesis and lipolysis. High levels of cortisol reduce the sensitivity of muscle and adipocytes to insulin as well. In fact, unusually high levels of cortisol (such as in Cushing’s syndrome) lead to insulin-resistance and type 2 diabetes mellitus.

Growth hormone

Growth hormone is secreted by the anterior pituitary gland and levels are higher when the body is stressed. Its effects are similar to those of cortisol in that it makes muscle and adipocytes less sensitive to the glucose uptake-promoting effects of insulin. Growth hormone also makes adipocytes more responsive to glucagon and increases gluconeogenesis by the liver.

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