Contribution of cortisol to glucose counterregulation in humans

Abstract

To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of cortisol increase caused a approximately 22% decrease in hepatic glucose production (P less than 0.01) and a approximately 15% increase in peripheral glucose utilization (P less than 0.01), which resulted in greater hypoglycemia (37 +/- 2 vs. 52 +/- 2 mg/dl, P less than 0.01) despite compensatory increases in plasma epinephrine. Lack of cortisol response also reduced plasma free fatty acid, beta-hydroxybutyrate, and glycerol concentrations approximately 50%. We conclude that cortisol normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle

“…In man, administration of dexamethasone decreased whole-body insulinstimulated glucose oxidation (measured with glucose-insulin clamps and indirect calorimetry) ; this decrease was considered secondary to the increase in plasma levels of non-esterified fatty acids [42]. Previous studies have shown that glucocorticoids increase the rate of lipolysis, suggesting that insulin resistance in muscle may be caused by the increased oxidation of non-esterified fatty acids [17,43]. Although, in i o, such a possibility is likely to play a role, the present results suggest that this may not be the main mechanism by which glucocorticoids induce insulin resistance.…”

Rat liver responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia

“…Thus, it is not clear whether the higher hepatic glucose production during IIH can be attributed to the improved capacity of the liver to produce glucose and/or to the enhanced availability of gluconeogenic substrates, since the concentration of glucose precursors increases (12,17,18) or decreases (8,(19)(20)(21) during IIH, depending on the experimental condition. To clarify this question and to overcome the limitations of in vivo experiments, we employed isolated liver from fasted rats which received a saturating concentration of gluconeogenic substrates at constant flow.…”

Glikokortykosteroidy a czynność komórek beta

“…Glikokortykosteroidy znacząco wpływają na metabolizm węglowodanów, lipidów i białek [1]. W okresach postu umożliwiają utrzymanie fizjologicznych stężeń glukozy we krwi poprzez zmniejszenie jej wychwytu i wykorzystania w mięśniach oraz przez stymulację wątrobowej produkcji glukozy (glukoneogeneza i glikogenoliza) [2]. Nadmiar GKS -spowodowany guzami przysadki, ektopowym wydzielaniem hormonu adrenokortykotropowego (ACTH, adrenocorticotropic hormone) guzami nadnerczy, albo pochodzenia egzogennego -prowadzi do licznych efektów niepożądanych, obejmujących otyłość trzewną, upośledzoną homeostazę glukozy, dyslipidemię oraz nadciśnienie tętnicze [3].…”

“…Moreover, GCs seriously influence carbohydrate, lipid, and protein metabolism [1]. During periods of fasting they enable maintenance of physiological blood glucose levels by decreasing glucose uptake and utilisation in muscle and by stimulating hepatic glucose production (gluconeogenesis and glycogenolysis) [2]. However, GC excess -caused either by pituitary tumours, ectopic ACTH secretion, adrenal tumours, or of exogenous origin -leads to several adverse effects, comprising visceral obesity, impaired glucose homeostasis, dyslipidaemia, and hypertension [3].…”