Underexpression of β cell high Km glucose transporters in noninsulin-dependent diabetes

John H. Johnson, Atsushi Ogawa, Ling Chen, Lelio Orci, Christopher B. Newgard, Tausif Alam, Roger H Unger

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Abstract

The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The β cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of β cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in β cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.

Original languageEnglish (US)
Pages (from-to)546-549
Number of pages4
JournalScience
Volume250
Issue number4980
StatePublished - Oct 26 1990

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Facilitative Glucose Transport Proteins
Glucose
Type 2 Diabetes Mellitus
Hyperglycemia
3-O-Methylglucose
Insulin
Messenger RNA
Islets of Langerhans

ASJC Scopus subject areas

  • General

Cite this

Johnson, J. H., Ogawa, A., Chen, L., Orci, L., Newgard, C. B., Alam, T., & Unger, R. H. (1990). Underexpression of β cell high Km glucose transporters in noninsulin-dependent diabetes. Science, 250(4980), 546-549.

Underexpression of β cell high Km glucose transporters in noninsulin-dependent diabetes. / Johnson, John H.; Ogawa, Atsushi; Chen, Ling; Orci, Lelio; Newgard, Christopher B.; Alam, Tausif; Unger, Roger H.

In: Science, Vol. 250, No. 4980, 26.10.1990, p. 546-549.

Research output: Contribution to journalArticle

Johnson, JH, Ogawa, A, Chen, L, Orci, L, Newgard, CB, Alam, T & Unger, RH 1990, 'Underexpression of β cell high Km glucose transporters in noninsulin-dependent diabetes', Science, vol. 250, no. 4980, pp. 546-549.
Johnson JH, Ogawa A, Chen L, Orci L, Newgard CB, Alam T et al. Underexpression of β cell high Km glucose transporters in noninsulin-dependent diabetes. Science. 1990 Oct 26;250(4980):546-549.
Johnson, John H. ; Ogawa, Atsushi ; Chen, Ling ; Orci, Lelio ; Newgard, Christopher B. ; Alam, Tausif ; Unger, Roger H. / Underexpression of β cell high Km glucose transporters in noninsulin-dependent diabetes. In: Science. 1990 ; Vol. 250, No. 4980. pp. 546-549.
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abstract = "The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19{\%} of controls. The β cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60{\%} of β cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in β cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.",
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