title: Neuronostatin inhibits glucose-stimulated insulin secretion via direct action on the pancreatic α-cell.
abstract: 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.
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri; and.
authors.forename: Alison S
authors.initials: AS
authors.lastname: Salvatori
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri; and.
authors.forename: Mollisa M
authors.initials: MM
authors.lastname: Elrick
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri; and.
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: John A
authors.initials: JA
authors.lastname: Corbett
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri; and gyosten@slu.edu.
authors.forename: Gina L C
authors.initials: GL
authors.lastname: Yosten
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001920:Bradykinin / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; C554543:neuronostatin protein, rat; D013004:Somatostatin; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D001920:Bradykinin
keywords: glucagon; glucose homeostasis; islet function; neuronostatin
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