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

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.24.9953· OSTI ID:5016961

Orci, L; Ravazzola, M; Baetens, D; Amherdt, M ^[1]; Inman, L; Johnson, J H; Unger, R H ^[2]; Peterson, R G ^[3]; Newgard, C B ^[4]

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1. Univ. of Geneva Medical School (Switzerland)
2. Univ. of Texas Southwestern Medical Center, Dallas (United States) Dept. of Veterans Affairs Medical Center, Dallas, TX (United States)
3. Univ. of Indiana School of Medicine, Indianapolis (United States)
4. Univ. of Texas Southwestern Medical Center, Dallas (United States)

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, the authors have previously reported profound underexpression of GLUT-2, the high-K{sub m} facilitative glucose transporter expressed by {beta} cells of normal animals. Here they report that islets of diabetic rats exhibit a marked decrease in the volume density 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. They 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.

• OSTI ID: 5016961
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:24; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLUCOSE
MEMBRANE TRANSPORT
HYPERGLYCEMIA
PATHOGENESIS
INSULIN
SENSITIVITY
MEMBRANE PROTEINS
TRANSMISSION ELECTRON MICROSCOPY
DIABETES MELLITUS
FLUORESCENCE
PANCREAS
ALDEHYDES
BODY
CARBOHYDRATES
DIGESTIVE SYSTEM
DISEASES
ELECTRON MICROSCOPY
ENDOCRINE DISEASES
ENDOCRINE GLANDS
GLANDS
HEXOSES
HORMONES
LUMINESCENCE
METABOLIC DISEASES
MICROSCOPY
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PROTEINS
SACCHARIDES
550201* - Biochemistry- Tracer Techniques