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    KU-32, a Novel Drug for Diabetic Neuropathy, is Safe for Human Islets and Improves in vitro Insulin Secretion and Viability

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    DobrwoskyR_ED_2012(671673).pdf (3.187Mb)
    Issue Date
    2012-12-01
    Author
    Farmer, Kevin L.
    Williams, S. Janette
    Novikova, Lesya
    Ramachandran, Karthik
    Rawal, Sonia
    Blagg, Brian S. J.
    Dobrowsky, Rick T.
    Stehno-Bittel, Lisa
    Publisher
    Hindawi Publishing Corporation
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
    Show full item record
    Abstract
    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.
    Description
    This is the publisher's version, also available electronically from "http://www.hindawi.com".
    URI
    http://hdl.handle.net/1808/17669
    DOI
    https://doi.org/10.1155/2012/671673
    Collections
    • Pharmacy Scholarly Works [286]
    Citation
    Farmer, K., Williams, S. J., Novikova, L., Ramachandran, K., 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, 2012, 1-11. http://dx.doi.org/10.1155/2012/671673

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    KU Libraries
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    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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