title: Progressive glucose stimulation of islet beta cells reveals a transition from segregated to integrated modular functional connectivity patterns.
abstract: Collective beta cell activity in islets of Langerhans is critical for the supply of insulin within an organism. Even though individual beta cells are intrinsically heterogeneous, the presence of intercellular coupling mechanisms ensures coordinated activity and a well-regulated exocytosis of insulin. In order to get a detailed insight into the functional organization of the syncytium, we applied advanced analytical tools from the realm of complex network theory to uncover the functional connectivity pattern among cells composing the intact islet. The procedure is based on the determination of correlations between long temporal traces obtained from confocal functional multicellular calcium imaging of beta cells stimulated in a stepwise manner with a range of physiological glucose concentrations. Our results revealed that the extracted connectivity networks are sparse for low glucose concentrations, whereas for higher stimulatory levels they become more densely connected. Most importantly, for all ranges of glucose concentration beta cells within the islets form locally clustered functional sub-compartments, thereby indicating that their collective activity profiles exhibit a modular nature. Moreover, we show that the observed non-linear functional relationship between different network metrics and glucose concentration represents a well-balanced setup that parallels physiological insulin release.
authors.affiliation: Faculty of Natural Sciences and Mathematics, University of Maribor, Koroška cesta 160, 2000 Maribor, Slovenia.
authors.forename: Rene
authors.initials: R
authors.lastname: Markovič
authors.affiliation: 1] Institute of Physiology, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia [2] Centre for Open Innovations and Research, University of Maribor, Slomškov trg 15, 2000 Maribor, Slovenia.
authors.forename: Andraž
authors.initials: A
authors.lastname: Stožer
authors.affiliation: 1] Faculty of Natural Sciences and Mathematics, University of Maribor, Koroška cesta 160, 2000 Maribor, Slovenia [2] Centre for Open Innovations and Research, University of Maribor, Slomškov trg 15, 2000 Maribor, Slovenia [3] Faculty of Education, University of Maribor, Koroška cesta 160, 2000 Maribor, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Gosak
authors.affiliation: Institute of Physiology, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia.
authors.forename: Jurij
authors.initials: J
authors.lastname: Dolenšek
authors.affiliation: 1] Faculty of Natural Sciences and Mathematics, University of Maribor, Koroška cesta 160, 2000 Maribor, Slovenia [2] Centre for Open Innovations and Research, University of Maribor, Slomškov trg 15, 2000 Maribor, Slovenia [3] Faculty of Education, University of Maribor, Koroška cesta 160, 2000 Maribor, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Marhl
authors.affiliation: 1] Institute of Physiology, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia [2] Centre for Open Innovations and Research, University of Maribor, Slomškov trg 15, 2000 Maribor, Slovenia [3] Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, A-1090 Vienna, Austria.
authors.forename: Marjan Slak
authors.initials: MS
authors.lastname: Rupnik
mesh_terms: D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D018613:Microscopy, Confocal
chemical_list: D005947:Glucose; D002118:Calcium