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

Atsushi Ogawa, John H. Johnson, Makoto Ohneda, Chris T. McAllister, Lindsey Inman, Tausif Alam, Roger H Unger

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113 Citations (Scopus)

Abstract

The roles of insulin resistance and β-cell dysfunction in glucocorticoid-induced diabetes were determined in Wistar and Zocker (fa/fa) rats. Al Wistar rats treated with 5 mg/kg per d of dexamethasone for 24 d exhibited increased β-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 β-cell transporter, GLUT-2, was present in ∼ 100% of β-cells of normoglycemic rats, but in only 25% of β 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 β cells of diabetic rats were GLUT-2-positive compared with ∼ 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 β cells are reduced, high Km glucose transport into β cells is attenuated and the insulin response to glucose is absent.

Original languageEnglish (US)
Pages (from-to)497-504
Number of pages8
JournalJournal of Clinical Investigation
Volume90
Issue number2
StatePublished - 1992

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Dexamethasone
Insulin Resistance
Glucose
Insulin
Hyperglycemia
Messenger RNA
Glucocorticoids
Arginine
Wistar Rats
Pancreas

Keywords

  • β-cell function
  • Dexamethanone
  • Diabetes
  • GLUT-2
  • Insulin resistance

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ogawa, A., Johnson, J. H., Ohneda, M., McAllister, C. T., Inman, L., Alam, T., & Unger, R. H. (1992). Roles of insulin resistance and β-cell dysfunction in dexamethasone-induced diabetes. Journal of Clinical Investigation, 90(2), 497-504.

Roles of insulin resistance and β-cell dysfunction in dexamethasone-induced diabetes. / Ogawa, Atsushi; Johnson, John H.; Ohneda, Makoto; McAllister, Chris T.; Inman, Lindsey; Alam, Tausif; Unger, Roger H.

In: Journal of Clinical Investigation, Vol. 90, No. 2, 1992, p. 497-504.

Research output: Contribution to journalArticle

Ogawa, A, Johnson, JH, Ohneda, M, McAllister, CT, Inman, L, Alam, T & Unger, RH 1992, 'Roles of insulin resistance and β-cell dysfunction in dexamethasone-induced diabetes', Journal of Clinical Investigation, vol. 90, no. 2, pp. 497-504.
Ogawa A, Johnson JH, Ohneda M, McAllister CT, Inman L, Alam T et al. Roles of insulin resistance and β-cell dysfunction in dexamethasone-induced diabetes. Journal of Clinical Investigation. 1992;90(2):497-504.
Ogawa, Atsushi ; Johnson, John H. ; Ohneda, Makoto ; McAllister, Chris T. ; Inman, Lindsey ; Alam, Tausif ; Unger, Roger H. / Roles of insulin resistance and β-cell dysfunction in dexamethasone-induced diabetes. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 2. pp. 497-504.
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