Pancreatic β-cell heterogeneity in adult human islets and stem cell-derived islets

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(6)

Published: June 1, 2023

Abstract Recent studies reported that pancreatic β-cells are heterogeneous in terms of their transcriptional profiles and abilities for insulin secretion. Sub-populations have been identified based on the functionality expression specific surface markers. Under diabetes condition, β-cell identity is altered leading to different sub-populations. Furthermore, cell–cell contact between other endocrine cells within islet play an important role regulating This highlights significance generating a cell product derived from stem containing along with major treating patients diabetes, instead transplanting purified population β-cells. Another key question how close heterogeneity cells? In this review, we summarize adult pancreas those generated cells. addition, highlight health disease conditions can be used design cell-derived therapy.

Language: Английский

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The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 28, 2023

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role diabetes mellitus. Cyclic adenosine monophosphate (cAMP) amplifies stimulus-secretion via protein kinase A guanine nucleotide exchange 2 (Epac2A). With the present research, we aimed to clarify influence of cAMP-elevating diterpene forskolin on cytoplasmic calcium dynamics intercellular network activity, which are two crucial elements normal beta cell coupling, Epac2A under stimulated conditions. To end, performed functional multicellular imaging mouse pancreas tissue slices after wild-type knock-out mice. Forskolin evoked signals otherwise substimulatory from mice displayed faster activation. During plateau phase, slightly higher active time response compared littermates, increased an increase oscillation frequency decrease duration both Functional properties during did not differ mice, but presence was for protective effect preventing decline connectivity time. Finally, prolonged activity deactivation, especially

Language: Английский

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Spatial distribution of heterogeneity as a modulator of collective dynamics in pancreatic beta-cell networks and beyond

Frontiers in Network Physiology, Journal Year: 2023, Volume and Issue: 3

Published: March 24, 2023

We study the impact of spatial distribution heterogeneity on collective dynamics in gap-junction coupled beta-cell networks comprised cells from two populations that differ their intrinsic excitability. Initially, these are uniformly and randomly distributed throughout networks. develop apply an iterative algorithm for perturbing arrangement network such same population increasingly likely to be adjacent one another. find global input strength, or drive, necessary transition a state quiescence synchronised oscillatory activity decreases as sortedness increases. Moreover, weak coupling, we regimes partial synchronisation wave propagation arise, which depend both drive sortedness. then demonstrate utility this studying general networks, use Watts-Strogatz case study. This work highlights importance node establishing rhythms complex, excitable has implications wide range real-world systems exhibit heterogeneity.

Language: Английский

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Multilevel synchronization of human β-cells networks

Frontiers in Network Physiology, Journal Year: 2023, Volume and Issue: 3

Published: Sept. 22, 2023

β -cells within the endocrine pancreas are fundamental for glucose, lipid and protein homeostasis. Gap junctions between cells constitute primary coupling mechanism through which synchronize their electrical metabolic activities. This evidence is still only partially investigated models numerical simulations. In this contribution, we explore effect of combined in -cell clusters using a detailed biophysical model. We add heterogeneity stochasticity to realistically reproduce dynamics study networks mimicking arrangements human pancreatic islets. Model simulations performed over different couplings heterogeneities, analyzing emerging synchronization at membrane potential, calcium, metabolites levels. To describe network synchronization, use formalism multiplex investigate functional properties motifs structural, electrical, layers. Our results show that can support slow wave propagation islets, realized small aggregates, long-range correlation more pronounced with respect one.

Language: Английский

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Geometric and topological characterization of the cytoarchitecture of islets of Langerhans

PLoS Computational Biology, Journal Year: 2023, Volume and Issue: 19(11), P. e1011617 - e1011617

Published: Nov. 9, 2023

The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta alpha cells, respectively, responsible for metabolic switching between fat glucose utilization. Dysfunction their secretion and/or counter-regulatory influence leads to diabetes. Debate the field centers on cytoarchitecture islets, as signaling governs hormonal depends structural functional factors, including electrical connectivity, innervation, vascularization, physical proximity. Much effort has therefore been devoted elucidating which architectural features significant function how derangements these correlated or causative dysfunction, especially using quantitative network science graph theory characterizations. Here, we ask if there non-local islet cytoarchitecture, going beyond standard statistics, relevant function. An example is ring structures, cycles, α δ cells surrounding β cell clusters opposite, cells. These could appear two-dimensional section images a sphere consisting one type surrounds cluster another type. To address issues, developed two independent computational approaches, geometric topological, such For latter, introduce an application topological data analysis determine locations biologically significant. We show both applied large collection sections, complete agreement context developmental diabetes-related changes characteristics. approach can be three-dimensional imaging well.

Language: Английский

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Calcium Imaging and Analysis in Beta Cells in Acute Mouse Pancreas Tissue Slices

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 223 - 246

Published: Oct. 12, 2024

Language: Английский

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