Driving Exocytosis with the Dual Oscillator Model

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NIDDK	BIOPHY-3

Authors

• J. Ha
• R. Bertram
• A. Sherman

Abstract

We extend our model for exocytosis of insulin from pancreatic beta cells (Pedersen and Sherman, PNAS 106:7432-6 2009) by coupling it to the Dual Oscillator Model (DOM), which describes oscillations in beta-cell electrical activity, calcium, and metabolism. The DOM can produce a range of oscillation periods from seconds to minutes, which allows us to study the effects of these oscillations on insulin secretion. This was examined previously by forcing the exocytosis model with membrane potential clamped to a waveform that resembled the oscillations seen in islets and the metabolic amplifying factor set independently of electrical activity. In the combined model we can look at the joint effects of metabolism and calcium when they are constrained to the dynamics they exhibit in order to produce the integrated response of the cells. We confirm a finding of the earlier forced exocytosis model that fast and slow oscillations produce similar mean levels of secretion but the slower oscillations produce higher peak levels of secretion. We examine whether this may be important for pancreatic communication with the liver, which likely filters out fast oscillations but responds to slow oscillations, by further coupling the secretion model with a model for insulin action.

back to top