Roles of insulin resistance and beta-cell dysfunction in dexamethasone-induced diabetes

J Clin Invest. 1992 Aug;90(2):497-504. doi: 10.1172/JCI115886.


The roles of insulin resistance and beta-cell dysfunction in glucocorticoid-induced diabetes were determined in Wistar and Zucker (fa/fa) rats. All Wistar rats treated with 5 mg/kg per d of dexamethasone for 24 d exhibited increased beta-cell mass and basal and arginine-stimulated insulin secretion, indicating insulin resistance, but only 16% became diabetic. The insulin response to 20 mM glucose was normal in the perfused pancreas of all normoglycemic dexamethasone-treated rats but absent in every diabetic rat. Immunostainable high Km beta-cell transporter, GLUT-2, was present in approximately 100% of beta-cells of normoglycemic rats, but in only 25% of beta cells of diabetic rats. GLUT-2 mRNA was not reduced. All Zucker (fa/fa) rats treated with 0.2-0.4 mg/kg per d of dexamethasone for 24 d became diabetic and glucose-stimulated insulin secretion was absent in all. High Km glucose transport in islets was 50% below nondiabetic controls. Only 25% of beta cells of diabetic rats were GLUT-2-positive compared with approximately 100% in controls. Total pancreatic GLUT-2 mRNA was increased twofold suggesting a posttranscriptional abnormality. We conclude that dexamethasone induces insulin resistance, whether or not it induces hyperglycemia. Whenever hyperglycemia is present, GLUT-2-positive beta cells are reduced, high Km glucose transport into beta cells is attenuated and the insulin response to glucose is absent.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Dexamethasone / pharmacology*
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / physiopathology
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Glucose / metabolism
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin Resistance*
  • Islets of Langerhans / physiopathology*
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • RNA, Messenger / genetics
  • Rats
  • Secretory Rate / drug effects


  • Insulin
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Dexamethasone
  • Glucose