Proteins altered by elevated levels of palmitate or glucose implicated in impaired glucose-stimulated insulin secretion
2009 (English)In: Proteome Science, ISSN 1477-5956, Vol. 7, 24- p.Article in journal (Refereed) Published
Development of type 2 diabetes mellitus (T2DM) is characterized by deranged insulin secretory patterns, where elevated insulin levels at non-stimulatory basal conditions and reduced hormonal levels at stimulatory conditions are major components. To delineate mechanisms responsible for these alterations we cultured INS-1E cells for 48 hours at 20 mM glucose in absence or presence of 0.5 mM palmitate, when stimulatory release was reduced or basal secretion was elevated, respectively.
After culture, cells were protein profiled by SELDI-TOF MS and 2D-PAGE. Differentially expressed proteins were discovered and identified by peptide mass fingerprinting. Complimentary protein profiles were obtained by the two approaches with SELDI-TOF MS being more efficient in separating proteins in the low molecular range and 2D-PAGE in the high molecular range. Identified proteins included alpha glucosidase, calmodulin, gars, glucose-6-phosphate dehydrogenase, heterogenous nuclear ribonucleoprotein A3, lon peptidase, nicotineamide adenine dinucleotide hydrogen (NADH) dehydrogenase, phosphoglycerate kinase, proteasome p45, rab2, pyruvate kinase and t-complex protein. The observed glucose-induced differential protein expression pattern indicates enhanced glucose metabolism, defense against reactive oxygen species, enhanced protein translation, folding and degradation and decreased insulin granular formation and trafficking. Palmitate-induced changes were related to altered exocytosis.
The identified altered proteins indicate mechanism important for deranged b-cell function in T2DM.
Place, publisher, year, edition, pages
2009. Vol. 7, 24- p.
insulin release, proteome profiling, SELDI-TOF MS, two-dimensional gel electrophoresis, type 2 diabetes mellitus
Medical and Health Sciences
Research subject Medical Cell Biology
IdentifiersURN: urn:nbn:se:uu:diva-98362DOI: 10.1186/1477-5956-7-24ISI: 000269306000001OAI: oai:DiVA.org:uu-98362DiVA: diva2:174251