Item type:Thesis, Open Access

Untersuchungen der Struktur-Wirkungsbeziehung zwischen GLP-1 und dem GLP-1 Rezeptor mit Hilfe von Site-directed Mutagenesis des GLP-1 Rezeptors und des Glukagon Rezeptors

Thumbnail Image

Files

dafi.pdf (919.91 KB)

Date

2007-07-12

relationships.isAuthorOf

Publisher

Philipps-Universität Marburg
DOI

item.page.supervisor-of-thesis

Abstract

The problems to treat diabetes melltius are not solved yet. The hormone GLP-1(7-36)amid is a promissing candidate for the pharmacological treatment of diabetes mellitus. It has a lot of positive qualities and very little side effects compared to other antidiabetic medications. It does not lead to hypoglycemia. But it has a very short halflife and its intestinal absorbtion rate is poor. Therefore it is important to evaluate the structure-reactivity relation of GLP-1 and its receptor to be able to develope analogas usable for therapy. For this evaluation 2 rezeptor chimera and 2 hormon chimera were constructed: [I197]-GLP-1 receptor and [K195]glucagon receptor in which the the lysin at position 197 of the GLP-1 receptor was switched with the isoleucin at position 195 of the glucagon receptor, and [Q9]-GLP-1 and [E3]-glucagon in which the glutamin acid and glutamin at position 3 of the two hormones were switched. With these chimera and the wildtyp receptors and hormones binding assays and cAMP assays were done to evaluate the structure-reactivity relation between them. These experiments showed that the carboxy-element of the glutamin acid at position 3 of GLP-1 is essentiell for GLP-1 receptor coupled cellactivation. It was demonstrated that isoleucin at positon 195 of the glucagon receptor is also important for glucagon receptor coupled cellactivation. Glutamin at position 3 of glucagon is not essentiell for intracellualar cAMP production and does not interact specifically with isoleucin at position 195 of the glucagon receptor.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2007Issued: 2007-07-12Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2007.0387
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
GLP-1Diabetes mellitusGLP-1 RezeptorG-ProteinGLP-1GLP-1 receptorTherapy
DFG-subjects
Diabetes mellitusPharmakotherapie
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2007.0387
show more
Fürniß-Ihns, Anna: Untersuchungen der Struktur-Wirkungsbeziehung zwischen GLP-1 und dem GLP-1 Rezeptor mit Hilfe von Site-directed Mutagenesis des GLP-1 Rezeptors und des Glukagon Rezeptors. : Philipps-Universität Marburg 2007-07-12. DOI: https://doi.org/10.17192/z2007.0387.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright