COEXISTENCE OF THREE OSCILLATORY MODES OF INSULIN SECRETION: MATHEMATICAL MODELING AND RELEVANCE TO GLUCOSE REGULATION

Abstract

Insulin secretion in pancreatic [Formula: see text]-cells exhibits three oscillatory modes with distinct period ranges, called fast, slow, and ultradian modes. To unveil the mechanism underlying such oscillatory behaviors and their roles in blood glucose regulation, we propose a combined model for the glucose–insulin regulation system, incorporating both the cell-level insulin secretion mechanism and inter-organ interactions in the blood glucose regulation. Special emphasis is placed on the identification of the mechanism of the slow oscillation and its role associated with the whole-body glucose regulation. Via extensive numerical simulations, we obtain macroscopic behaviors of the three types of insulin/glucose oscillations in the whole-body as well as microscopic behaviors of the membrane potential and the calcium concentration in the [Formula: see text]-cell. Finally, optimal regulatory strategies for the blood glucose level are discussed on the basis of the quantitative information obtained from the mathematical modeling and numerical simulations.