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bioRxiv · 10.1101/2024.08.21.608986

δ-α cell-to-cell interactions modulate pancreatic islet Ca2+ oscillation modes

Tang, C.·Ren, H.·Li, Y.·Xie, B.·Qian, W.·Yu, Y.·Chang, T.·Yang, X.·sneppen, k.·Chen, L.
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Abstract

Glucose-induced pancreatic islet hormone release is tightly coupled with oscillations in cytoplasmic free Ca2+ concentration of islet cells, which is regulated by a complex interplay between intercellular and intracellular signaling. {delta} cells, which entangle with cells located at the islet periphery, are known to be important paracrine regulators. However, the role of {delta} cells in regulating Ca2+ oscillation pattern remains unclear. Here we show that {delta}- cell-to-cell interactions are the source of variability in glucose-induced Ca2+ oscillation pattern. Somatostatin secreted from {delta} cells prolonged the islets oscillation period in an cell mass-dependent manner. Pharmacological and optogenetic perturbations of {delta}- interactions led islets to switch between fast and slow Ca2+ oscillations. Continuous adjustment of {delta}- coupling strength caused the fast oscillating islets to transition to mixed and slow oscillations. We developed a mathematical model, demonstrating that the fast-mixed-slow oscillation transition is a Hopf bifurcation. Our findings provide a comprehensive understanding of how {delta} cells modulate islet Ca2+ dynamics and reveal the intrinsic heterogeneity of islets due to the structural composition of different cell types. HighlightsO_LISomatostatin slows down islet Ca2+ oscillations in an cell mass-dependent manner. C_LIO_LIPharmacological and optogenetic perturbations of {delta}- interaction cause islet Ca2+ oscillation mode switching. C_LIO_LIContinuous tuning of {delta}- interaction strength induces fast-mixed-slow oscillation transition successively. C_LIO_LIMathematical modeling shows the fast-mixed-slow oscillation transition as a Hopf bifurcation. C_LI

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Tang, C., Ren, H., Li, Y., Xie, B., Qian, W., Yu, Y., Chang, T., Yang, X., sneppen, k., Chen, L.. 2024-08-22. δ-α cell-to-cell interactions modulate pancreatic islet Ca2+ oscillation modes. https://doi.org/10.1101/2024.08.21.608986

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