Neuronostatin acts via GPR107 to increase cAMP-independent PKA phosphorylation and proglucagon mRNA accumulation in pancreatic α-cells. Am J Physiol Regul Integr Comp Physiol 2016 Jan 15;310(2):R143-55
Date
11/13/2015Pubmed ID
26561648Pubmed Central ID
PMC4796643DOI
10.1152/ajpregu.00369.2014Scopus ID
2-s2.0-84983172665 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
Neuronostatin (NST) is a recently described peptide that is produced from the somatostatin preprohormone in pancreatic δ-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 α-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 α-cells. Compromise of GPR107 in pancreatic α-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 α-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 α-cells.
Author List
Elrick MM, Samson WK, Corbett JA, Salvatori AS, Stein LM, Kolar GR, Naatz A, Yosten GLAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Line
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Glucagon-Secreting Cells
Humans
Male
Mice
Peptide Fragments
Peptide Hormones
Phosphorylation
Proglucagon
RNA Interference
RNA, Messenger
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled
Signal Transduction
Somatostatin
Transfection
Up-Regulation
