Evidence that down-regulation of β-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia

L. Orci, M. Ravazzola, D. Baetens, L. Inman, M. Amherdt, R. G. Peterson, C. B. Newgard, J. H. Johnson, Roger H Unger

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Abstract

Non-insulin-dependent diabetes mellitus (NIDDM) is attributed to a failure of pancreatic β cells to maintain insulin secretion at a level sufficient to compensate for underlying insulin resistance. In the ZDF rat, a model of NIDDM that closely resembles the human syndrome, we have previously reported profound underexpression of GLUT-2, the high-Km facultative glucose transporter expressed by β cells of normal animals. Here we report that islets of diabetic rats exhibit a marked decrease in the volume density of GLUT-2-positive β cells and a reduction at the electron-microscopic level in the number of GLUT-2-immunoreactive sites per unit of β-cell plasma membrane. The deficiency of GLUT-2 cannot be induced in normal β cells by in vivo or in vitro exposure to high levels of glucose nor can it be prevented in β cells of prediabetic ZDF rats by elimination of hyperglycemia. We conclude that this dearth of immunodetectable GLUT-2 in NIDDM is not secondary to hyperglycemia and therefore that it may well play a causal role in the development of hyperglycemia.

Original languageEnglish (US)
Pages (from-to)9953-9957
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number24
StatePublished - 1990

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Facilitative Glucose Transport Proteins
Hyperglycemia
Down-Regulation
Type 2 Diabetes Mellitus
Cell Membrane
Insulin Resistance
Electrons
Insulin
Glucose

ASJC Scopus subject areas

  • Genetics
  • General

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Evidence that down-regulation of β-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia. / Orci, L.; Ravazzola, M.; Baetens, D.; Inman, L.; Amherdt, M.; Peterson, R. G.; Newgard, C. B.; Johnson, J. H.; Unger, Roger H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 24, 1990, p. 9953-9957.

Research output: Contribution to journalArticle

Orci, L. ; Ravazzola, M. ; Baetens, D. ; Inman, L. ; Amherdt, M. ; Peterson, R. G. ; Newgard, C. B. ; Johnson, J. H. ; Unger, Roger H. / Evidence that down-regulation of β-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia. In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 24. pp. 9953-9957.
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AU - Orci, L.

AU - Ravazzola, M.

AU - Baetens, D.

AU - Inman, L.

AU - Amherdt, M.

AU - Peterson, R. G.

AU - Newgard, C. B.

AU - Johnson, J. H.

AU - Unger, Roger H

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