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

Journal Article (Journal Article)

Non-insulin-dependent diabetes mellitus (NIDDM) is attributed to a failure of pancreatic beta 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 facilitative glucose transporter expressed by beta cells of normal animals. Here we report that islets of diabetic rats exhibit a marked decrease in the volume of GLUT-2-positive beta cells and a reduction at the electron-microscopic level in the number of GLUT-2-immunoreactive sites per unit of beta-cell plasma membrane. The deficiency of GLUT-2 cannot be induced in normal beta cells by in vivo or in vitro exposure to high levels of glucose nor can it be prevented in beta 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.

Full Text

Duke Authors

Cited Authors

  • Orci, L; Ravazzola, M; Baetens, D; Inman, L; Amherdt, M; Peterson, RG; Newgard, CB; Johnson, JH; Unger, RH

Published Date

  • December 1990

Published In

Volume / Issue

  • 87 / 24

Start / End Page

  • 9953 - 9957

PubMed ID

  • 2263645

Pubmed Central ID

  • PMC55292

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.87.24.9953


  • eng

Conference Location

  • United States