Andraž Stožer (Avtor), Maša Skelin (Avtor), Marko Gosak (Avtor), Lidija Križančić Bombek (Avtor), Viljem Pohorec (Avtor), Marjan Rupnik (Avtor), Jurij Dolenšek (Avtor)

Povzetek

Many details of glucose-stimulated intracellular calcium changes in [beta] cells during activation, activity, and deactivation, as well as their concentration-dependence, remain to be analyzed. Classical physiological experiments indicated that in islets, functional differences between individual cells are largely attenuated, but recent findings suggest considerable intercellular heterogeneity, with some cells possibly coordinating the collective responses. To address the above with an emphasis on heterogeneity and describing the relations between classical physiological and functional network properties, we performed functional multicellular calcium imaging in mouse pancreas tissue slices over a wide range of glucose concentrations. During activation, delays to activation of cells and any-cell-to-first-responder delays are shortened, and the sizes of simultaneously responding clusters increased with increasing glucose concentrations. Exactly the opposite characterized deactivation. The frequency of fast calcium oscillations during activity increased with increasing glucose up to 12 mM glucose concentration, beyond which oscillation duration became longer, resulting in a homogenous increase in active time. In terms of functional connectivity, islets progressed from a very segregated network to a single large functional unit with increasing glucose concentration. A comparison between classical physiological and network parameters revealed that the first-responders during activation had longer active times during plateau and the most active cells during the plateau tended to deactivate later. Cells with the most functional connections tended to activate sooner, have longer active times, and deactivate later. Our findings provide a common ground for recent differing views on [beta] cell heterogeneity and an important baseline for future studies of stimulus-secretion and intercellular coupling. NEW & NOTEWORTHY We assessed concentration-dependence in coupled [beta] cells, degree of functional heterogeneity, and uncovered possible specialized subpopulations during the different phases of the response to glucose at the level of many individual cells. To this aim, we combined acute mouse pancreas tissue slices with functional multicellular calcium imaging over a wide range from threshold (7 mM) and physiological (8 and 9 mM) to supraphysiological (12 and 16 mM) glucose concentrations, classical physiological, and advanced network analyses.

Ključne besede

beta cells;calcium imaging;glucose-dependence;network analysis;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UM MF - Medicinska fakulteta
Založnik: American Physiological Society
UDK: 612
COBISS: 75400451 Povezava se bo odprla v novem oknu
ISSN: 0193-1849
Št. ogledov: 0
Št. prenosov: 0
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: beta celice;kalcijevo slikanje;glukozna odvisnost;
Vrsta dela (COBISS): Znanstveno delo
Strani: str. E305-E323
Letnik: ǂVol. ǂ321
Zvezek: ǂiss. ǂ2
Čas izdaje: 2021
DOI: 10.1152/ajpendo.00043.2021
ID: 25300887