GLUT-2 function in glucose-unresponsive β cells of dexamethasone-induced diabetes in rats

Makoto Ohneda, John H. Johnson, Lindsey R. Inman, Roger H Unger

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Spontaneous and dexamethasone-induced noninsulin-dependent diabetes mellitus (NIDDM) in rats is associated with loss of glucose-stimulated insulin secretion (GSIS) and a reduction in both GLUT-2-positive β cells and high Km glucose transport. To determine if the chronology and correlation of these abnormalities is consistent with a causal relationship, Zucker (fa/fa) rats were studied longitudinally before and during 10 d of dexamethasone-induced (0.4 mg/kg per d i.p.) NIDDM. Within 24 h of dexamethasone treatment blood glucose rose and GSIS declined, becoming paradoxically negative (-87 ± 12 μU /ml per min) on day 10. Blood glucose was negatively correlated with GSIS (r = -0.92; P < 0.001 ). 3-0-methyl-D-glucose (3MG) transport was unchanged at 12 h, 23% below normal on day 1, and declined further to a nadir 59% below normal. The GLUT-2-positive β cell area did not decline until 48 h, reaching a nadir of 35% of normal at 10 d. The area of GLUT-2-positive β cells was correlated with GSIS (r = 0.77; P < 0.005). We conclude that the chronology and correlation between GSIS loss and hyperglycemia is consistent with a cause-effect relationship, but that the subtotal impairment in glucose transport by itself cannot explain the total loss of GSIS if one assumes that normal β cells are functionally homogenous.

Original languageEnglish (US)
Pages (from-to)1950-1956
Number of pages7
JournalJournal of Clinical Investigation
Volume92
Issue number4
StatePublished - 1993

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Dexamethasone
Glucose
Insulin
Chronology
Type 2 Diabetes Mellitus
Blood Glucose
Hyperglycemia

Keywords

  • β cells, glucose-stimulated insulin secretion
  • GLUT-2
  • Islet glucose transport
  • Noninsulin-dependent diabetes mellitus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

GLUT-2 function in glucose-unresponsive β cells of dexamethasone-induced diabetes in rats. / Ohneda, Makoto; Johnson, John H.; Inman, Lindsey R.; Unger, Roger H.

In: Journal of Clinical Investigation, Vol. 92, No. 4, 1993, p. 1950-1956.

Research output: Contribution to journalArticle

Ohneda, Makoto ; Johnson, John H. ; Inman, Lindsey R. ; Unger, Roger H. / GLUT-2 function in glucose-unresponsive β cells of dexamethasone-induced diabetes in rats. In: Journal of Clinical Investigation. 1993 ; Vol. 92, No. 4. pp. 1950-1956.
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