title: Signaling in insulin-secreting MIN6 pseudoislets and monolayer cells.
abstract: Cell-cell interactions are of fundamental importance for cellular function. In islets of Langerhans, which control blood glucose levels by secreting insulin in response to the blood glucose concentration, the secretory response of intact islets is higher than that of insulin-producing beta-cells not arranged in the islet architecture. The objective was to define mechanisms by which cellular performance is enhanced when cells are arranged in three-dimensional space. The task was addressed by making a comprehensive analysis based on protein expression patterns generated from insulin-secreting MIN6 cells grown as islet-like clusters, so-called pseudoislets, and in monolayers. After culture, glucose-stimulated insulin secretion (GSIS) was measured from monolayers and pseudoislets. GSIS rose 6-fold in pseudoislets but only 3-fold in monolayers when the glucose concentration was increased from 2 to 20 mmol/L. Proteins from pseudoislets and monolayers were extracted and analyzed by liquid-chromatography mass spectrometry, and differentially expressed proteins were mapped onto KEGG pathways. Protein profiling identified 1576 proteins, which were common to pseudoislets and monolayers. When mapped onto KEGG pathways, 11 highly enriched pathways were identified. On the basis of differences in expression of proteins belonging to the pathways in pseudoislets and monolayers, predictions of differential pathway activation were performed. Mechanisms enhancing insulin secretory capacity of the beta-cell, when situated in the islet, include pathways regulating glucose metabolism, cell interaction, and translational regulation.
authors.affiliation: Department of Medical Cell Biology, Uppsala University , Box 571, SE-75123 Uppsala, Sweden.
authors.forename: Azazul
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Venkata P
authors.initials: VP
authors.lastname: Satagopam
authors.forename: Levon
authors.initials: L
authors.lastname: Manukyan
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Artemenko
authors.forename: Yi Man Eva
authors.initials: YM
authors.lastname: Fung
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneider
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.forename: Peter
authors.initials: P
authors.lastname: Bergsten
mesh_terms: D000818:Animals; D002450:Cell Communication; D018929:Cell Culture Techniques; D002853:Chromatography, Liquid; D015870:Gene Expression; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D058977:Molecular Sequence Annotation; D015398:Signal Transduction
chemical_list: D007328:Insulin; D005947:Glucose