Pancreatic alpha and beta cells are globally phase-locked
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Pancreatic alpha and beta cells are globally phase-locked. / Ren, Huixia; Li, Yanjun; Han, Chengsheng; Yu, Yi; Shi, Bowen; Peng, Xiaohong; Wu, Shufang; Yang, Xiaojing; Kim, Sneppen; Chen, Liangyi; Tang, Chao; Zhang, Tianming.
In: Nature Communications, Vol. 13, No. 1, 3721, 28.06.2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Pancreatic alpha and beta cells are globally phase-locked
AU - Ren, Huixia
AU - Li, Yanjun
AU - Han, Chengsheng
AU - Yu, Yi
AU - Shi, Bowen
AU - Peng, Xiaohong
AU - Wu, Shufang
AU - Yang, Xiaojing
AU - Kim, Sneppen
AU - Chen, Liangyi
AU - Tang, Chao
AU - Zhang, Tianming
PY - 2022/6/28
Y1 - 2022/6/28
N2 - The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic alpha and beta cells play a crucial role in glucose homeostasis. However, how alpha and beta cells coordinate to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice, we recorded Ca2+ signals from islet alpha and beta cells, and observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a brief period of glucose stimulation, alpha and beta cells' oscillations were globally phase-locked. While the activation of alpha cells displayed a fixed time delay of similar to 20 s to that of beta cells, beta cells activated with a tunable period. Moreover, islet a 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.
AB - The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic alpha and beta cells play a crucial role in glucose homeostasis. However, how alpha and beta cells coordinate to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice, we recorded Ca2+ signals from islet alpha and beta cells, and observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a brief period of glucose stimulation, alpha and beta cells' oscillations were globally phase-locked. While the activation of alpha cells displayed a fixed time delay of similar to 20 s to that of beta cells, beta cells activated with a tunable period. Moreover, islet a 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.
KW - PULSATILE INSULIN-SECRETION
KW - GLUCAGON-SECRETION
KW - CA2+ OSCILLATIONS
KW - ELECTRICAL-ACTIVITY
KW - MOUSE ISLETS
KW - SUSTAINED OSCILLATIONS
KW - PLASMA-INSULIN
KW - BASAL INSULIN
KW - CYCLIC-AMP
KW - GLUCOSE
U2 - 10.1038/s41467-022-31373-6
DO - 10.1038/s41467-022-31373-6
M3 - Journal article
C2 - 35764654
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3721
ER -
ID: 315261532