Sökning: onr:"swepub:oai:DiVA.org:uu-406692" >
Molecular Imaging o...
Molecular Imaging of Diabetic Kidney Tissue and Binding Studies of Proinsulin C-peptide
-
- Lindfors, Lina (författare)
- Uppsala universitet,Organisk kemi
-
- Kihlberg, Jan, Professor (preses)
- Uppsala universitet,Organisk kemi
-
- Lanekoff, Ingela, Assoc. Prof. 1975- (preses)
- Uppsala universitet,Analytisk kemi
-
visa fler...
-
- Almqvist, Fredrik, Professor (opponent)
- Umeå Universitet, Kemiska institutionen
-
visa färre...
-
(creator_code:org_t)
- ISBN 9789151309149
- Uppsala : Acta Universitatis Upsaliensis, 2020
- Engelska 54 s.
-
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 ; 1920
- Relaterad länk:
-
https://uu.diva-port... (primary) (Raw object)
-
visa fler...
-
https://uu.diva-port... (Preview)
-
https://urn.kb.se/re...
-
visa färre...
Abstract
Ämnesord
Stäng
- Diabetic kidney disease is a serious complication of diabetes with a complex and incompletely understood pathology. In this work, the molecular changes in diabetic rat kidneys at a very early disease stage were studied using nanospray desorption electrospray ionisation mass spectrometry imaging. Our results demonstrate how disease-relevant metabolites and lipids can be conveniently analysed on intact kidney tissue sections. A number of significantly increased metabolites were identified in the diabetic kidney, revealing disturbances in energy metabolism detectable before histological changes.Proinsulin C-peptide is produced in the pancreas along with insulin and has shown beneficial effects in diabetes, but its mode of action is not yet known. 125I radiolabelled C-peptide was used to study its tissue distribution in healthy and diabetic rats after intravenous injection. The majority of C-peptide accumulated in renal tissues, with lower levels in the diabetic animals, showing that there are significant changes in kidney – C-peptide interactions in early stage diabetes.The interactions of C-peptide with the orphan receptor GPR146, which has been proposed as its receptor, were also investigated using Chinese hamster ovary cells overexpressing human GPR146. Neither dynamic mass redistribution nor β-arrestin recruitment assays showed any significant response to human or murine C-peptides in the GPR146 overexpressing cells compared to controls. Fluorescence confocal microscopy revealed no surface binding or cellular uptake of C-peptides by GPR146 overexpressing cells compared to controls. These combined results refute the suggestion that GPR146 is the C-peptide receptor.To further probe the function of C-peptide, 15N-labelled residues were incorporated into the peptide in preparation for nanoscale secondary ion mass spectrometry imaging of cells and intact kidney tissue sections. A number of crosslinking C-peptides were also designed and synthesised for experiments aimed at identifying its binding target. These studies have not yet been completed. Finally, to investigate the structure-activity relationship of C-peptide, a library of modified pentapeptide analogues was created for medium-throughput testing in a cell assay.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Analytisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Analytical Chemistry (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- Diabetic kidney disease
- Proinsulin C-peptide
- GPR146
- Mass spectrometry imaging
- nano-DESI
- Kemi
- Chemistry
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
Hitta via bibliotek
Till lärosätets databas