Neuronostatin inhibits glucose-stimulated insulin secretion via direct action on the pancreatic α-cell. Am J Physiol Endocrinol Metab 2014 Jun 01;306(11):E1257-63
Date
04/17/2014Pubmed ID
24735892Pubmed Central ID
PMC4042099DOI
10.1152/ajpendo.00599.2013Scopus ID
2-s2.0-84901710347 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Neuronostatin is a recently described peptide hormone encoded by the somatostatin gene. We previously showed that intraperitoneal injection of neuronostatin into mice resulted in c-Jun accumulation in pancreatic islets in a pattern consistent with the activation of glucagon-producing α-cells. We therefore hypothesized that neuronostatin could influence glucose homeostasis via a direct effect on the α-cell. Neuronostatin enhanced low-glucose-induced glucagon release in isolated rat islets and in the immortalized α-cell line αTC1-9. Furthermore, incubation with neuronostatin led to an increase in transcription of glucagon mRNA, as determined by RT-PCR. Neuronostatin also inhibited glucose-stimulated insulin secretion from isolated islets. However, neuronostatin did not alter insulin release from the β-cell line INS 832/13, indicating that the effect of neuronostatin on insulin secretion may be secondary to a direct action on the α-cell. In agreement with our in vitro data, intra-arterial infusion of neuronostatin in male rats delayed glucose disposal and inhibited insulin release during a glucose challenge. These studies suggest that neuronostatin participates in maintaining glucose homeostasis through cell-cell interactions between α-cells and β-cells in the endocrine pancreas, leading to attenuation in insulin secretion.
Author List
Salvatori AS, Elrick MM, Samson WK, Corbett JA, 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
AnimalsArea Under Curve
Blood Glucose
Blotting, Western
Bradykinin
Cell Line
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Electrophoresis, Polyacrylamide Gel
Glucagon-Secreting Cells
Glucose
Injections, Intraperitoneal
Inositol 1,4,5-Trisphosphate
Insulin
Islets of Langerhans
Male
Peptide Fragments
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Somatostatin
