Table 2.

Pathophysiological mechanisms of glucocorticoid-associated hyperglycemia

Pathophysiological mechanisms

Increase endogenous glucose production (hepatic gluconeogenesis)

Impaired insulin sensitivity (antagonizing metabolic actions of insulin)

Reduce insulin-mediated actions on muscle and adipose tissue:

Reduce peripheral glucose uptake

Decrease GLUT-4 translocation to cell membrane

Decrease muscle glycogen synthesis[13]

Post-receptor insulin signaling defect

Enhance the effects of other counter-regulatory hormones (glucagon and epinephrine) that increase endogenous gluconeogenesis

Inhibit the production and secretion of insulin from pancreatic β-cells

Reduction of β-cell GLUT-2 and glucokinase receptor expression

Increasing activity of glucose-6-phosphate dehydrogenase

Alteration in β-oxidation

Reduce the effect of incretins on β-cell to decrease insulin secretion

Lipotoxicity-induced β-cell failure indirectly (induce lipolysis elevating triglycerides and free fatty acids)

Expression of the nuclear receptor peroxisome proliferator-activated receptor α is altered