Evidence that down-regulation of beta-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia
| Autor: | R. G. Peterson, D. Baetens, Roger H Unger, Lelio Orci, Mariella Ravazzola, Christopher B. Newgard, John H. Johnson, M. Amherdt, Lindsey Inman |
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| Rok vydání: | 1990 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Monosaccharide Transport Proteins endocrine system diseases medicine.medical_treatment Fluorescent Antibody Technique Biology Diabetes Mellitus Experimental Islets of Langerhans Insulin resistance Downregulation and upregulation Reference Values Internal medicine Diabetes mellitus medicine Animals Microscopy Immunoelectron Beta (finance) Multidisciplinary Microvilli Insulin Cell Membrane Glucose transporter nutritional and metabolic diseases Rats Inbred Strains medicine.disease Rats Rats Zucker medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 2 Hyperglycemia Female Beta cell Pancreas hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 87:9953-9957 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.87.24.9953 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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