Regulation of GAD expression in rat pancreatic islets and brain by gamma-vinyl-GABA and glucose
| Autor: | K. Rimvall, Thomas Dyrberg, P. N. Jørgensen, Kim Ry Hejnaes, A. J. Moody, Jacob S. Petersen, J. T. Clausen, E. Hasselager |
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| Rok vydání: | 1998 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Carboxy-lyases endocrine system diseases Endocrinology Diabetes and Metabolism Glutamate decarboxylase Biology Vigabatrin GABA transaminase Islets of Langerhans In vivo Antibody Specificity Internal medicine Internal Medicine medicine Animals Enzyme Inhibitors Rats Wistar Cells Cultured gamma-Aminobutyric Acid geography geography.geographical_feature_category Glutamate Decarboxylase Pancreatic islets nutritional and metabolic diseases Brain Islet Rats Isoenzymes medicine.anatomical_structure Endocrinology Glucose Enzyme inhibitor Enzyme Induction biology.protein Pancreas |
| Zdroj: | Diabetologia. 41(5) |
| ISSN: | 0012-186X |
| Popis: | Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM), but little is known about its regulation and function in islet cells. We investigated the effects of the GABA-transaminase inhibitor gamma-vinyl-GABA (GVG) on GAD expression in rat islets and brain in vitro and in vivo. In islets incubated in high glucose culture medium there was an increase in GAD activity, GAD65 and GAD67 protein levels compared to low-glucose conditions; however, even in high glucose, GVG still significantly suppressed GAD activity and GAD67 expression. Our observations suggest that glucose and GVG act on GAD in islets through different mechanisms. Quantitative immunohistochemistry of pancreatic sections from rats treated with GVG in vivo using novel monoclonal antibodies specific for GAD65 and GAD67, showed a decrease in GAD67 expression (p < 0.005) relative to untreated rats. The effects of GVG on rat pancreatic islets were very similar to those observed in brain of rats treated with GVG in vivo. In homogenates of cerebral tissue from GVG treated rats containing both membrane-bound and soluble protein GAD67 levels were significantly decreased while GAD65 levels were not significantly changed compared to untreated rats. In contrast, in homogenates of cerebral tissues containing only soluble cytosolic protein, GVG-treatment was also significantly found to decrease GAD65 levels. Taken together, these results suggest that GVG potentially could be of use to decrease GAD expression in islet cells and consequently to deviate/inhibit the autoimmune response against the beta cells seen in IDDM. |
| Databáze: | OpenAIRE |
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