KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability
Joint Authors
Rawal, Sonia
Williams, S. Janette
Novikova, Lesya
Ramachandran, Karthik
Dobrowsky, Rick
Stehno-Bittel, Lisa
Farmer, Kevin
Blagg, Brian S. J.
Source
Experimental Diabetes Research
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-11-01
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
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 the in vitro viability 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 the in vivo metabolic parameters of diabetic mice.
American Psychological Association (APA)
Farmer, Kevin& Williams, S. Janette& Novikova, Lesya& Ramachandran, Karthik& Rawal, Sonia& Blagg, Brian S. J.…[et al.]. 2012. KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability. Experimental Diabetes Research،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-489220
Modern Language Association (MLA)
Farmer, Kevin…[et al.]. KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability. Experimental Diabetes Research No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-489220
American Medical Association (AMA)
Farmer, Kevin& Williams, S. Janette& Novikova, Lesya& Ramachandran, Karthik& Rawal, Sonia& Blagg, Brian S. J.…[et al.]. KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability. Experimental Diabetes Research. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-489220
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-489220