Insulin deprivation decreases insulin degrading enzyme levels in primary cultured cortical neurons and in the cerebral cortex of rats with streptozotocin-induced diabetes
| Autor: | Nihan Burul-Bozkurt, Inci Kazkayasi, Angel Cedazo-Minguez, Can Pekiner, Muhammad-Al-Mustafa Ismail, Serdar Uma, Paula Merino-Serrais |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Time Factors medicine.medical_treatment Primary Cell Culture Insulysin Diabetes Mellitus Experimental 03 medical and health sciences 0302 clinical medicine Western blot Internal medicine Diabetes mellitus medicine Insulin-degrading enzyme Animals Insulin Incubation Cerebral Cortex Neurons Pharmacology Dose-Response Relationship Drug medicine.diagnostic_test Chemistry General Medicine medicine.disease Streptozotocin Rats Cortex (botany) Glucose 030104 developmental biology medicine.anatomical_structure Endocrinology Cerebral cortex 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pharmacological Reports. 70:677-683 |
| ISSN: | 1734-1140 |
| Popis: | Background Many studies have indicated a relationship between diabetes and Alzheimer’s disease (AD). However, the molecular mechanism underlying this association has not been clarified. Among several factors, insulin degrading enzyme (IDE), which plays roles in the degradation of both insulin and amyloid β (Aβ), has gained interest as a potential target in efforts to solve this puzzle. This study sought to examine the effects of varying insulin and/or glucose concentrations on IDE expression. Methods Experiments were performed on primary cultured rat neurons and cortices of rats with streptozotocin (STZ)-induced diabetes. IDE protein and mRNA expression levels were measured by western blot and RT-PCR, respectively. Results In primary cultured cortical neurons, removal of insulin for 5 days reduced the expression of IDE. A five-day treatment with a high concentration of glucose in insulin-free media reduced IDE levels, while a high concentration of glucose in the presence of insulin had no effect. In groups treated with glucose or insulin intermittently, the reduction in IDE levels was observed only in neurons exposed to high glucose together with no insulin for 5 days. Shorter incubation periods (48 h), either continuously or intermittently, did not affect IDE levels. IDE expression in the cortex of rats with STZ-induced diabetes was found to be decreased. Conclusion Our data suggest that insulin deprivation, rather than high glucose, is a significant determinant of IDE regulation. As evidence indicates potential roles for IDE in diabetes and AD, understanding the mechanisms regulating IDE expression may be important in developing new treatment strategies. |
| Databáze: | OpenAIRE |
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