• Deutsch
    • English
  • English 
    • Deutsch
    • English
  • Login
Item View 
  •   Home
  • Medizin
  • Molekulare Medizin
  • Item View
  •   Home
  • Medizin
  • Molekulare Medizin
  • Item View
JavaScript is disabled for your browser. Some features of this site may not work without it.

Role of Pax6 in pancreatic endocrine cell subtype specification

by Zeeshan Ahmad
Doctoral thesis
Date of Examination:2013-05-17
Date of issue:2014-03-27
Advisor:Prof. Dr. Ahmed Mansouri
Referee:Prof. Dr. Wolfgang Engel
Referee:Prof. Dr. Ralf Dressel
crossref-logoPersistent Address: http://dx.doi.org/10.53846/goediss-4432

 

 

Files in this item

Name:Ahmad Z Thesis.pdf
Size:4.07Mb
Format:PDF
ViewOpen

The following license files are associated with this item:


Abstract

English

Pax6, a transcription factor from the paired box gene family is expressed in the endocrine pancreas and is required for its proper development. As Pax6 classical and pancreas-specific conditional knockout mice die early after birth, it is not possible to analyze the role of Pax6 in adult endocrine cell function. Therefore, we generated non-inducible alpha-cell-specific and inducible beta-cell-specific Pax6 knockout mice to observe the cell-type-specific effect of Pax6 ablation. Following Pax6 ablation, the adult beta-cells lost their mature differentiation state and function. This was evident by the reduced expression of insulin, MafA, Nkx6.1, Glut2, and GLP-1 receptor and an increased expression of proSAAS and 7B2. Loss of beta-cell function in turn resulted in hyperglycemia in these mice. Furthermore, these Pax6-deficient beta-cells started to express ghrelin and persisted in the islets as immature beta-cell-like cells. Ablation of Pax6 from alpha-cells also resulted in the loss of mature alpha-cell function that was evident by the reduced expression of glucagon and MafB and an increased expression of 7B2. Pax6-deficient alpha-cells also started to express ghrelin. In this study, we confirmed the essential requirement of Pax6 in adult alpha- and beta-cell function in vivo and clearly established the origin of ghrelin+ cells in the respective Pax6 knockout pancreata. Moreover, when overexpressed in the pancreas, Pax6 did not affect the development or function of beta-cells but the numbers of alpha-, PP-, and epsilon-cells were slightly reduced.
Keywords: Pancreas; Endocrine; Pax6; Insulin; Glucagon; Ghrelin
 

Statistik

Publish here

Browse

All of eDissFaculties & ProgramsIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesTypeThis FacultyIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesType

Help & Info

Publishing on eDissPDF GuideTerms of ContractFAQ

Contact Us | Impressum | Cookie Consents | Data Protection Information
eDiss Office - SUB Göttingen (Central Library)
Platz der Göttinger Sieben 1
Mo - Fr 10:00 – 12:00 h


Tel.: +49 (0)551 39-27809 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
ediss_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]
Göttingen State and University Library | Göttingen University
Medicine Library (Doctoral candidates of medicine only)
Robert-Koch-Str. 40
Mon – Fri 8:00 – 24:00 h
Sat - Sun 8:00 – 22:00 h
Holidays 10:00 – 20:00 h
Tel.: +49 551 39-8395 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
bbmed_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]