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Pancreatic α and β cells are globally phase-locked.

ABSTRACT: The Ca²⁺ modulated pulsatile glucagon and insulin secretions by pancreatic α and β cells play a crucial role in glucose homeostasis. However, how α and β cells coordinate to produce various Ca²⁺ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice, we recorded Ca²⁺ signals from islet α and β cells, and observed heterogeneous Ca²⁺ oscillation patterns intrinsic to each islet. After a brief period of glucose stimulation, α and β cells' oscillations were globally phase-locked. While the activation of α cells displayed a fixed time delay of ~20 s to that of β cells, β cells activated with a tunable period. Moreover, islet α cell number correlated with oscillation frequency. We built a mathematical model of islet Ca²⁺ oscillation incorporating paracrine interactions, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction in generating stable but tunable islet oscillation patterns.

SUBMITTER: Ren H

PROVIDER: S-EPMC9240067 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Pancreatic α and β cells are globally phase-locked.

Ren Huixia H Li Yanjun Y Han Chengsheng C Yu Yi Y Shi Bowen B Peng Xiaohong X Zhang Tianming T Wu Shufang S Yang Xiaojing X Kim Sneppen S Chen Liangyi L Tang Chao C

Nature communications 20220628 1

The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic α and β cells play a crucial role in glucose homeostasis. However, how α and β cells coordinate to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice, we recorded Ca2+ signals from islet α and β cells, and observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a brief period of glucose stimulation, ...[more]

PMID: 35764654

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Project description:microRNAs (miRNAs) play an important role in pancreatic development and adult ?-cell physiology. Our hypothesis is based on the assumption that each islet cell type has a specific pattern of miRNA expression. We sought to determine the profile of miRNA expression in ?-and ?-cells, the main components of pancreatic islets, because this analysis may lead to a better understanding of islet gene regulatory pathways. Highly enriched (>98%) subsets of human ?-and ?-cells were obtained by flow cytometric sorting after intracellular staining with c-peptide and glucagon antibody. The method of sorting based on intracellular staining is possible because miRNAs are stable after fixation. MiRNA expression levels were determined by quantitative high throughput PCR-based miRNA array platform screening. Most of the miRNAs were preferentially expressed in ?-cells. From the total of 667 miRNAs screened, the Significant Analysis of Microarray identified 141 miRNAs, of which only 7 were expressed more in ?-cells (?-miRNAs) and 134 were expressed more in ?-cells (?-miRNAs). Bioinformatic analysis identified potential targets of ?-miRNAs analyzing the Beta Cell Gene Atlas, described in the T1Dbase, the web platform, supporting the type 1 diabetes (T1D) community. cMaf, a transcription factor regulating glucagon expression expressed selectively in ?-cells (TF?) is targeted by ?-miRNAs; miR-200c, miR-125b and miR-182. Min6 cells treated with inhibitors of these miRNAs show an increased expression of cMaf RNA. Conversely, over expression of miR-200c, miR-125b or miR-182 in the mouse alpha cell line ?TC6 decreases the level of cMAF mRNA and protein. MiR-200c also inhibits the expression of Zfpm2, a TF? that inhibits the PI3K signaling pathway, at both RNA and protein levels.In conclusion, we identified miRNAs differentially expressed in pancreatic ?- and ?-cells and their potential transcription factor targets that could add new insights into different aspects of islet biology and pathophysiology.

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Pancreatic α and β cells are globally phase-locked.

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Pancreatic α and β cells are globally phase-locked.

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