[Novel aspects in the mechanisms of steroid diabetes and the regulation of hepatic glucose production by insulin and steroids].
Glucocorticoids are known to increase blood glucose levels, and an impairment of glucose tolerance is a common side effect of glucocorticoid therapy and a central feature of Cushing's disease. A major pathophysiological event in this process is an increased glucose production of the liver on the basis of glucocorticoid-induced insulin resistance resulting in an increment in hepatic gluconeogenesis. Both, glucocorticoids and insulin are known to affect the expression of the two gluconeogenic key enzymes, phosphoenolpyruvate-carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). While glucocorticoids are known to stimulate the expression of the PEPCK- and G6Pase gene, insulin decreases hepatic glucose production through an inhibition of PEPCK- and G6Pase gene expression. Recently, considerable progress has been made in the understanding of the signal transduction involved in the glucocorticoid- and insulin-dependent regulation of hepatic gluconeogenesis. In this article, we will review the most recent advances and assemble the current knowledge into a clinically relevant pathophysiological model.
Barthel
Andreas
A
Abteilung für Endokrinologie, Klinik für Innere Medizin der Heinrich-Heine-Universität Düsselfdorf. Andreas.Barthel@uni-duesseldorf.de
Scherbaum
Werner A
WA
Bornstein
Stefan R
SR
D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects*; D005943:Gluconeogenesis / Q000187:drug effects* / Q000235:genetics; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D001786:Blood Glucose; D005938:Glucocorticoids; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)