Electrical activity in pancreatic β-cells plays a pivotal role in glucose-stimulated insulin secretion by coupling metabolism to calcium-triggered exocytosis. Mathematical models based on rodent data have helped in understanding the mechanisms underlying the electrophysiological patterns observed in laboratory animals. However, human β-cells differ in several aspects, and in particular in their electrophysiological characteristics, from rodent β-cells. Hence, from a clinical perspective and to obtain insight into the defects in insulin secretion relevant for diabetes mellitus, it is important to study human β-cells. This work presents the first mathematical model of electrical activity based entirely on published ion channel characteristics of human β-cells. The model reproduces satisfactorily a series of experimentally observed patterns in human β-cells, such as spiking and rapid bursting electrical activity, and their response to a range of ion channel antagonists. The possibility of Human Ether-a-Go-Go-related- and leak channels as drug targets for diabetes treatment is discussed based on model results.
A Biophysical Model of Electrical Activity in Human beta-Cells
PEDERSEN, MORTEN GRAM
2010
Abstract
Electrical activity in pancreatic β-cells plays a pivotal role in glucose-stimulated insulin secretion by coupling metabolism to calcium-triggered exocytosis. Mathematical models based on rodent data have helped in understanding the mechanisms underlying the electrophysiological patterns observed in laboratory animals. However, human β-cells differ in several aspects, and in particular in their electrophysiological characteristics, from rodent β-cells. Hence, from a clinical perspective and to obtain insight into the defects in insulin secretion relevant for diabetes mellitus, it is important to study human β-cells. This work presents the first mathematical model of electrical activity based entirely on published ion channel characteristics of human β-cells. The model reproduces satisfactorily a series of experimentally observed patterns in human β-cells, such as spiking and rapid bursting electrical activity, and their response to a range of ion channel antagonists. The possibility of Human Ether-a-Go-Go-related- and leak channels as drug targets for diabetes treatment is discussed based on model results.
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