KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    IDENTIFYING MECHANISMS OF INSULIN PRODUCTION AND SECRETION IN SMALL AND LARGE RAT ISLETS

    Thumbnail
    View/Open
    Huang_ku_0099D_11775_DATA_1.pdf (1.713Mb)
    Issue Date
    2011-12-31
    Author
    Huang, Han-Hung
    Publisher
    University of Kansas
    Format
    122 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Physical Therapy & Rehabilitation Sciences
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
    Metadata
    Show full item record
    Abstract
    The existence of islet subpopulations according to size difference has been described since 1869 when Dr. Paul Langerhans first discovered the islets in the pancreas. Unfortunately, little is known about the functional differences between islet subpopulations until recently. Small islets have been shown to secret more insulin than large islets per volume (islet equivalent; IE) and led to better transplantation outcome both in rodents and in humans. Insulin is produced and released from the beta cells in islets through a cascading pathway from insulin gene transcription to proinsulin biosynthesis to insulin secretion. The central hypothesis of this dissertation is that small and large islets have different characteristics in insulin production and secretion that lead to different transplantation outcomes. More than ten thousands small (diameter less or equal 100µm) and large (diameter above or equal 200µm) islets from healthy rats were investigated. First, the same percentage of beta cells was identified in small and large islets, but small islets had higher density both in vitro and in situ. Next, a new regression model was established to better estimate the islet volume by cell number based on size (diameter), since an overestimation was seen when using conventional IE measurement to normalize islet volume. By applying this new normalization method, a superior glucose-stimulated proinsulin biosynthesis was identified in large islets. However, when normalized to cell number, insulin secretion was not different between small and large islets, unlike the results in literature when normalized to IE. While small and large islets showed no difference in total protein content per cell, large islets showed higher protein levels of prosinulin, NeuroD/Beta2 and MafA with a lower PDX-1 level under basal conditions suggesting that the different characteristics between small and large islets in the insulin production pathway may not correspond to measured insulin secretion. All the findings will not only elucidate new intricacies concerning islet biology research, but also will have significant implications to current islet transplantation research to optimize the success for curing type 1 diabetes.
    URI
    http://hdl.handle.net/1808/9721
    Collections
    • Dissertations [4454]
    • KU Med Center Dissertations and Theses [464]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    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
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    Login

    Statistics

    View Usage Statistics

    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
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps