|Start Date / Time||March 12, 2014 at 9:00 AM|
|End Date / Time||March 12, 2014 at 9:55 AM|
|Location||512 Light Hall|
|Presenter Name||Amy Elliott (Piston)|
|Presentation Title||“Somatostatin and Insulin Mediate Glucose-Inhibited Glucagon Secretion in the Pancreatic α-Cell by Lowering cAMP”|
|Status||This meeting has already occurred|
The dysregulation of glucose-inhibited glucagon secretion from the pancreatic islet α-cell is a critical component of diabetes pathology and metabolic disease. We show a previously uncharacterized [Ca2+]i-independent mechanism of glucagon suppression in human and murine pancreatic islets whereby cAMP and PKA signaling is decreased. Furthermore, we show that this suppression arises from somatostatin preventing cAMP production by adenylyl cyclases via the Gαi subunit of the SSTR2 and from insulin receptor activation of phosphodiesterase 3B to drive degradation of cAMP in a glucose-dependent manner. Our data indicate that both somatostatin and insulin signaling is required to decrease cAMP and PKA sufficiently to inhibit glucagon secretion from islets and isolated α-cells. Thus, we conclude that somatostatin and insulin together are critical paracrine mediators of glucose-inhibited glucagon secretion and function by lowering cAMP/PKA signaling with increasing glucose.