EphA4 Receptor Forward Signaling Inhibits Glucagon Secretion From α-Cells.

ABSTRACT: The loss of inhibition of glucagon secretion exacerbates hyperglycemia in type 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 correlates with maintenance of a dense F-actin network. In islets, additional stimulation and inhibition of endogenous EphA forward signaling result in inhibition and enhancement, respectively, of glucagon secretion, accompanied by an increase and decrease, respectively, in α-cell F-actin density.

SUBMITTER: Hutchens T 

PROVIDER: S-EPMC4613968 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature