October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
A mathematical model for glucagon secretion from alpha cells
| Friday, November 08, 2013 — Poster Session IV | |||
|---|---|---|---|
2:00 p.m. – 4:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIDDK |
COMPBIO-21 |
Authors
- M. A. Watts
- A. S. Sherman
Abstract
Glucose homeostasis is largely controlled by alpha and beta cells located in pancreatic islets. Both of these cell types respond to blood glucose levels, albeit in an opposite manner. While beta cells secrete insulin when blood glucose is elevated, alpha cells secrete glucagon when blood glucose levels are low. The mechanism by which glucose induces insulin secretion in beta cells is fairly well understood. However, the mechanism of glucagon secretion is still not well established. It has been proposed that glucose can affect the alpha cell through effects on the conductance of ATP-dependent potassium channels (K(ATP)). An alternative theory asserts that glucose regulates glucagon secretion through a store-operated current (SOC). We developed a mathematical model to test these hypotheses and found that both mechanisms are possible. Glucose can suppress glucagon secretion by closing K(ATP) channels, which depolarizes the cells but paradoxically reduces calcium influx by inactivating voltage-dependent calcium channels. Glucose can also suppress glucagon secretion by activating SERCA pumps, which fills the endoplasmic reticulum and hyperpolarizes the cells by reducing the inward current through SOC channels. We suggest that both mechanisms contribute and that they can combine to account for the non-monotonic dependence of secretion on glucose.
