KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and ImprovesIn VitroInsulin Secretion and Viability
| العنوان: | KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and ImprovesIn VitroInsulin Secretion and Viability |
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| المؤلفون: | S. Janette Williams, Karthik Ramachandran, Lesya Novikova, Rick T. Dobrowsky, Lisa Stehno-Bittel, Sonia Rawal, Brian S. J. Blagg, Kevin L. Farmer |
| المصدر: | Experimental Diabetes Research Experimental Diabetes Research, Vol 2012 (2012) |
| بيانات النشر: | Hindawi Limited, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Blood Glucose, Male, Time Factors, Diabetic neuropathy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, lcsh:Medicine, Apoptosis, Type 2 diabetes, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Tissue Culture Techniques, Mice, 0302 clinical medicine, Diabetic Neuropathies, Insulin Secretion, Insulin, 0303 health sciences, Microscopy, Confocal, General Medicine, Middle Aged, 3. Good health, Neuroprotective Agents, medicine.anatomical_structure, Female, Beta cell, Pancreas, Novobiocin, Research Article, Adult, lcsh:Internal medicine, medicine.medical_specialty, lcsh:Specialties of internal medicine, Article Subject, Cell Survival, Biology, Islets of Langerhans, 03 medical and health sciences, lcsh:RC581-951, In vivo, Internal medicine, Diabetes mellitus, medicine, Animals, Humans, HSP90 Heat-Shock Proteins, lcsh:RC31-1245, 030304 developmental biology, lcsh:RC648-665, Dose-Response Relationship, Drug, Pancreatic islets, lcsh:R, medicine.disease, Disease Models, Animal, Endocrinology, Diabetes Mellitus, Type 2, 030217 neurology & neurosurgery |
| الوصف: | KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on thein vitroviability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter thein vivometabolic parameters of diabetic mice. |
| وصف الملف: | text/xhtml |
| تدمد: | 1687-5303 1687-5214 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8db59fe01d54efd0559f1cf4a9218a26Test https://doi.org/10.1155/2012/671673Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8db59fe01d54efd0559f1cf4a9218a26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16875303 16875214 |
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