title: Quantitative proteomics reveals the link between minichromosome maintenance complex and glucose-induced proliferation of rat pancreatic INS-1E β-cells.
abstract: Proper functioning of pancreatic β-cells is a crucial for glucose homeostasis control, and therefore a main problem regarding type 2 diabetes onset and evolution. The ability of β-cells to proliferate upon certain stimuli, such as elevated glucose concentration, is an essential property to overpass a major problem of the pathology: the decrease of β-cell mass leading to a lack of insulin production. However, high glucose concentrations are also an inducer of β-cell dysfunction, when proliferation become unable to overcome insulin demand. The control of β-cell proliferation could represent an interesting target for the development of therapeutic molecules for type 2 diabetes treatment. To get new insights on β-cell replication, we investigated the modulation of nuclear proteins of INS-1E cells submitted to medium and high glucose concentrations for 24h. Indeed, the nucleus should contain proteins responsible of proliferation-related events. The SILAC approach allowed us identifying 24 nuclear proteins whose expressions were modified by chronic high glucose. A wide Downstream Effects Analysis assigned the majority of the differentially expressed proteins to functions such as proliferation and cell cycle. Interestingly, our study linked for the first time the increase of expression of the 6 MCM components to glucose-induced stimulation in β-cells.
  
  
  CONCLUSIONS
  The current study represents a progress in the understanding of glucose-induced proliferation mechanisms in β-cells. We applied the SILAC strategy to INS-1E cells cultivated with medium or high glucose concentrations for 24h, and we targeted nuclear proteins which have a central role in proliferation-related mechanisms. It allows quantifying 24 nuclear proteins, which are regulated by high glucose exposure. The vast majority of them are shown to be related to proliferation and cell cycle. We describe here for the first time than the 6 proteins of the MCM complex are involved in glucose-mediated proliferation in β-cells.
authors.affiliation: Translational Biomarker Group, Department of Human Protein Sciences, University Medical Center, Geneva, Switzerland.
authors.forename: Domitille
authors.initials: D
authors.lastname: Schvartz
authors.affiliation: INSERM, U1038, Grenoble F-38054, France; CEA, iRTSV, Biologie à Grande Echelle, Grenoble F-38054, France; Université Grenoble-Alpes, Grenoble F-38000, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Couté
authors.affiliation: Translational Biomarker Group, Department of Human Protein Sciences, University Medical Center, Geneva, Switzerland. Electronic address: jean-charles.sanchez@unige.ch.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D013549:Sweetening Agents / Q000494:pharmacology*
chemical_list: D007328:Insulin; D013549:Sweetening Agents; D064110:Minichromosome Maintenance Proteins; D005947:Glucose
keywords: MiniChromosome maintenance complex; Nuclei; Proliferation; β-Cell