Current and ongoing beta cell research is presented in this weekly seminar by faculty, postdoctoral fellows and students. If you are interested in attending the Beta Cell Interest Group (BIG) seminars and joining the BIG community, please contact David Jacobson.

Keywords: beta cell BIG

Record History
Added on January 8, 2015 at 2:53 PM by Brown, Deborah
Modified on April 15, 2015 at 11:30 AM by Brown, Deborah
Shared with (contributions)
BIG: Beta Cell Interest Group (BIG) Master

Meeting Details

Start Date / Time April 29, 2015 at 9:00 AM
End Date / Time April 29, 2015 at 9:55 AM
Duration 55 minutes
Location 512 Light Hall
Presenter Name Troy Hutchens (Piston's lab)
Presentation Title EphA4-Mediated Juxtacrine Signaling Regulates Glucagon Secretion through Changes in F-Actin Density
Status This meeting has already occurred

Meeting Agenda/Notes

The loss of inhibition of glucagon secretion exacerbates hyperglycemia in types 1 and 2 diabetes.  However, the molecular mechanisms that regulate glucagon secretion in unaffected and diabetic states remain relatively unexplained.  We present evidence supporting a new model of juxtacrine-mediated regulation of glucagon secretion where neighboring islet cells negatively regulate glucagon secretion through tonic stimulation of α-cell EphA receptors.  Primarily through EphA4 receptors, this stimulation contributes to the maintenance of a dense F-actin network.  In islets, additional stimulation and inhibition of endogenous EphA forward signaling results in inhibition and enhancement, respectively, of glucagon secretion, accompanied by an increase and decrease, respectively, in α-cell F-actin density.  Sorted α-cells lack endogenous stimulation of EphA forward signaling from neighboring cells, resulting in enhanced basal glucagon secretion as compared to islets and the elimination of glucose-inhibition of glucagon secretion.  Restoration of EphA forward signaling in sorted α-cells recapitulates both normal basal glucagon secretion and glucose-inhibition of glucagon secretion.  Additionally, α-cell-specific EphA4-/- mice exhibit abnormal glucagon dynamics, and EphA4-/- α-cells contain less dense F-actin networks than EphA4+/+ α-cells.  This juxtacrine-mediated model provides insight into the functional and dysfunctional regulation of glucagon secretion and opens up new therapeutic strategies for the clinical management of diabetes.