| First Author | Elrick MM | Year | 2016 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 310 |
| Issue | 2 | Pages | R143-55 |
| PubMed ID | 26561648 | Mgi Jnum | J:230744 |
| Mgi Id | MGI:5763701 | Doi | 10.1152/ajpregu.00369.2014 |
| Citation | Elrick MM, et al. (2016) Neuronostatin acts via GPR107 to increase cAMP-independent PKA phosphorylation and proglucagon mRNA accumulation in pancreatic alpha-cells. Am J Physiol Regul Integr Comp Physiol 310(2):R143-55 |
| abstractText | Neuronostatin (NST) is a recently described peptide that is produced from the somatostatin preprohormone in pancreatic delta-cells. NST has been shown to increase glucagon secretion from primary rat pancreatic islets in low-glucose conditions. Here, we demonstrate that NST increases proglucagon message in alpha-cells and identify a potential mechanism for NST's cellular activities, including the phosphorylation of PKA following activation of the G protein-coupled receptor, GPR107. GPR107 is abundantly expressed in the pancreas, particularly, in rodent and human alpha-cells. Compromise of GPR107 in pancreatic alpha-cells results in failure of NST to increase PKA phosphorylation and proglucagon mRNA levels. We also demonstrate colocalization of GPR107 and NST on both mouse and human pancreatic alpha-cells. Taken together with our group's observation that NST infusion in conscious rats impairs glucose clearance in response to a glucose challenge and that plasma levels of the peptide are elevated in the fasted compared with the fed or fasted-refed state, these studies support the hypothesis that endogenous NST regulates islet cell function by interacting with GPR107 and initiating signaling in glucagon-producing alpha-cells. |
