Both cellular ATP level and ATP hydrolysis free energy determine energetically the calcium oscillation in pancreatic $\beta$-cell

TL;DR

This study models how cellular ATP levels and hydrolysis free energy influence calcium oscillations in pancreatic β-cells, crucial for insulin secretion, revealing energy thresholds necessary for proper oscillation function.

Contribution

We developed a kinetic thermodynamic model based on Betram et al. 2004 to analyze ATP's role in calcium oscillations in pancreatic β-cells, highlighting energy dependence.

Findings

Bifurcation points are sensitive to ATP levels and free energy.

Insufficient ATP energy disrupts calcium oscillation.

Energy thresholds are critical for oscillation stability.

Abstract

In pancreatic $\beta$-cells, calcium oscillation signal is the core part of glucose-stimulated insulin secretion. Intracellular calcium concentration oscillates in response to the intake of glucose, which triggers the exocytosis of insulin secretory granules. ATP plays a crucial part in this process. ATP increases as the result of glucose intake, then ATP binds to ATP-sensitive $K^+$ channels ($K_{ATP}$), depolarizes the cell and triggers calcium oscillation, while the ion pumps on the cell membrane consumes the free energy form ATP hydrolysis. Based on Betram et. al. 2004 model, we construct a kinetic models to analyze the thermodynamic characteristics of this system, to reveal how the ATP hydrolysis free energy affects the calcium oscillation. Our results suggest that bifurcation point is sensitive to both the free energy level and cellular ATP level, and the insufficient ATP energy supply would cause dysfunction of calcium oscillation.