Mitochondrial proteome analysis reveals altered expression of voltage dependent anion channels in pancreatic beta-cells exposed to high glucose
Author
Summary, in English
Chronic hyperglycemia leads to deterioration of insulin release from pancreatic beta-cells as well as insulin action on peripheral tissues. However, the mechanism underlying beta-cell dysfunction resulting from glucose toxicity has not been fully elucidated. The aim of the present study was to define a set of alterations in mitochondrial protein profiles of pancreatic beta-cell line in response to glucotoxic condition using 2-DE and tandem mass spectrometry. INS1E cells were incubated in the presence of 5.5 and 20 mM glucose for 72 hrs and mitochondria were isolated. Approximately 75 protein spots displayed significant changes (p < 0.05) in relative abundance in the presence of 20 mM glucose compared to controls. Mitochondrial proteins downregulated under glucotoxic conditions includes ATP synthase a chain and delta chain, malate dehydrogenase, aconitase, trifunctional enzyme beta subunit, NADH-cytochrome b5 reductase and voltage-dependent anion-selective channel protein (VDAC) 2. VDAC 1, 75 kDa glucose-regulated protein, heat shock protein (HSP) 60 and HSP10 were found to be upregulated. The orchestrated changes in expression of VDACs and multiple other proteins involved in nutrient metabolism, ATP synthesis, cellular defense, glycoprotein folding and mitochondrial DNA stability may explain cellular dysfunction in glucotoxicity resulting in altered insulin secretion.
Department/s
- Islet cell physiology
- EXODIAB: Excellence of Diabetes Research in Sweden
Publishing year
2010
Language
English
Pages
283-292
Publication/Series
Islets
Volume
2
Issue
5
Document type
Journal article
Publisher
Landes Bioscience
Topic
- Endocrinology and Diabetes
Keywords
- proteomics
- two-dimensional gel electrophoresis
- voltage-dependent
- anion-selective channel proteins
- mitochondria
- insulin secretion
- mass
- spectrometry
Status
Published
Research group
- Islet cell physiology
ISBN/ISSN/Other
- ISSN: 1938-2022