Cortisol increases gluconeogenesis in humans: its role in the metabolic syndrome

Abstract

Android obesity is associated with increased cortisol secretion. Direct effects of cortisol on gluconeogenesis and other parameters of insulin resistance were determined in normal subjects. Gluconeogenesis was determined using the reciprocal pool model of Haymond and Sunehag (HS method), and by the Cori cycle/lactate dilution method of Tayek and Katz (TK method). Glucose production (GP) and gluconeogenesis were measured after a 3 h baseline infusion and after a 4-8 h pituitary-pancreatic infusion of somatostatin, replacement insulin, growth hormone (GH), glucagon and a high dose of cortisol (hydrocortisone). The pituitary-pancreatic infusion maintains insulin, GH and glucagon concentrations within the fasting range, while increasing the concentration of only one hormone, cortisol. Two groups of five subjects were each given high-dose cortisol administration, and results were compared with those from a group of six 'fasting alone' subjects (no infusion) at 16 and 20 h of fasting. Fasting GP (12 h fasting) was similar in all groups, averaging 12.5+/-0.2 micromol x min(-1) x kg(-1). Gluconeogenesis, as a percentage of GP, was 35+/-2% using the HS method and 40+/-2% using the TK method. After 16 h of fasting, GP had fallen (11.5+/-0.6 micromol x min(-1) x kg(-1)) and gluconeogenesis had increased (55+/-5% and 57+/-5% of GP by the HS and TK methods respectively; P<0.05). High-dose cortisol infusion for 4 h increased serum cortisol (660+/-30 nmol/l; P<0.05), blood glucose (7.9+/-0.5 mmol/l; P<0.05) and GP (14.8+/-0.8 micromol x min(-1) x kg(-1); P<0.05). The increase in GP was due entirely to an increase in gluconeogenesis, determined by either the HS or the TK method (66+/-6% and 65+/-5% of GP respectively; P<0.05). Thus cortisol administration in humans increases GP by stimulating gluconeogenesis. Smaller increases in serum cortisol may contribute to the abnormal glucose metabolism known to occur in the metabolic syndrome.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

“…Glucagon, like epinephrine, leads to increased glucose production through both gluconeogenesis and glycogenolysis (81). The action of glucagon alone is not maintained over time; however, its action on gluconeogenesis is sustained in an additive manner with the presence of epinephrine, cortisol, and GH (74,81). Likewise, epinephrine and glucagon have an additive effect on glycogenolysis (81).…”

“…In critical illness, however, metabolic alterations can cause significant changes in energy substrate metabolism. To provide glucose, a major fuel source to vital organs, release of the above-mentioned stress mediators oppose the anabolic actions of insulin (74). By enhancing adipose tissue lipolysis (75) and skeletal muscle proteolysis (76), they increase gluconeogenic substrates, including glycerol, alanine, and lactate, thus augmenting hepatic glucose production in burn patients (72,73,77).…”

Variation in adrenal and thyroid hormones with life-history stage in juvenile northern elephant seals (Mirounga angustirostris)

“…Catecholamines, such as epinephrine and norepinephrine, are also released as part of the fight-or-flight response to stress. Together, the suite of hormones activated by this response influence many processes in the body including heart rate, metabolic rate, energy allocation, growth, reproduction, immune response, memory, and behavior, allowing an animal to react appropriately to the stress, which ultimately promotes survival (Breuner et al, 2013;Brilion et al, 1995;Connell and Davies, 2005;Khani and Tayek, 2001;Maule et al, 1987;Romero and Butler, 2007;Tilbrook et al, 2000).…”

The Hepatic Acute Phase Response to Thermal Injury

“…Glucagon, like epinephrine, leads to increased glucose production through both gluconeogenesis and glycogenolysis (81). The action of glucagons alone is not maintained over time; however, its action on gluconeogenesis is sustained in an additive manner with the presence of epinephrine, cortisol, and GH (74,81). Likewise, epinephrine and glucagon have an additive effect on glycogenolysis (81).…”

“…In critical illness, however, metabolic alterations can cause significant changes in energy substrate metabolism. In order to provide glucose, a major fuel source to vital organs, release of the above mentioned stress mediators oppose the anabolic actions of insulin (74). By enhancing adipose tissue lipolysis (75) and skeletal muscle proteolysis (76), they increase gluconeogenic substrates, including glycerol, alanine and lactate, thus augmenting hepatic glucose production in burned patients (72,73,77).…”