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Mitochondrial protein patterns correlating with impaired insulin secretion from INS‐1E cells exposed to elevated glucose concentrations
Author(s) -
Nyblom Hanna K.,
Thorn Kristofer,
Ahmed Meftun,
Bergsten Peter
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200600137
Subject(s) - differential centrifugation , mitochondrion , secretion , proteome , insulin , western blot , proteomics , endocrinology , biology , medicine , centrifugation , diabetes mellitus , cell , apoptosis , carbohydrate metabolism , biochemistry , gene
Extended hyperglycaemia leads to impaired glucose‐stimulated insulin secretion (GSIS) and eventually β‐cell apoptosis in individuals with type 2 diabetes mellitus. In an attempt to dissect mechanisms behind the detrimental effects of glucose, we focused on measuring changes in expression patterns of mitochondrial proteins. Impaired GSIS was observed from INS‐1E cells cultured for 5 days at 20 or 27 mM glucose compared to cells cultured at 5.5 or 11 mM glucose. After culture, mitochondria were isolated from the INS‐1E cells by differential centrifugation. Proteins of the mitochondrial fraction were bound to a strong anionic surface (SAX2) protein array and mass spectra generated by SELDI‐TOF‐MS. Analysis of the spectra revealed proteins with expression levels that correlated with the glucose concentration of the culture medium. Indeed, such differentially expressed proteins created patterns of protein changes, which correlated with impairment of GSIS. In conclusion, the study reveals the first glucose‐induced differentially expressed patterns of β‐cell mitochondrial proteins obtained by SELDI‐TOF‐MS.