Neuropeptide Y expression and regulation in a differentiated rat insulin-secreting cell line.

Details

Serval ID
serval:BIB_DB5EB17F4687
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neuropeptide Y expression and regulation in a differentiated rat insulin-secreting cell line.
Journal
Endocrinology
Author(s)
Waeber G., Thompson N., Waeber B., Brunner H.R., Nicod P., Grouzmann E.
ISSN
0013-7227
Publication state
Published
Issued date
1993
Peer-reviewed
Oui
Volume
133
Number
3
Pages
1061-7
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Neuropeptide-Y (NPY) is a 36-amino acid peptide known to inhibit glucose-stimulated insulin secretion in various animal models in vitro and in vivo. NPY is thought to be one of the mediators of sympathetic action in the pancreas through nerve endings surrounding the islets, and it has recently been shown to be synthesized within the islets of Langerhans. To elucidate the potential role of NPY in the endocrine pancreas, we studied the expression and regulation of NPY secretion in a rat insulinoma cell line (INS-1). NPY mRNA and peptide are highly expressed and secreted by INS-1 cells. NPY levels were determined by a sensitive and specific two-site amplified enzyme-linked immunosorbent assay. Incubation of INS-1 cells with various glucose concentrations did not modify NPY secretion; however, stimulation of adenylate cyclase by forskolin induced a dose- and time-dependent increase in NPY release in the medium. The glucagon-like peptide-I-(7-36) amide (GLP-1), a known gluco-incretin in humans, induced at low concentration (10(-9) M) a similar expression of NPY mRNA and peptide secretion in INS-1 cells. On the other hand, the inhibition of cAMP accumulation by the alpha 2-adrenergic agonist clonidine decreased NPY secretion. In conclusion, 1) high levels of gene expression and secretion of NPY are found in a rat insulinoma cell line (INS-1). 2) Accumulation of cAMP induced by forskolin or a gluco-incretin (GLP-1) induces a further increase in NPY gene expression and release. 3) NPY secretion is not modulated by low or high glucose concentrations in the medium. 4) Induction of NPY, a known inhibitor of insulin secretion, may represent a novel counterregulatory mechanism of insulin secretion, limiting the stimulatory effect of GLP-1 on insulin secretion.
Keywords
Adenylate Cyclase, Animals, Cell Differentiation, Clonidine, Cyclic AMP, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Forskolin, Gene Expression Regulation, Neoplastic, Glucagon, Glucagon-Like Peptide 1, Glucagon-Like Peptides, Insulin, Insulinoma, Neuropeptide Y, Pancreatic Neoplasms, Peptide Fragments, Protein Kinase C, Rats, Receptors, Neuropeptide Y, Tumor Cells, Cultured
Pubmed
Web of science
Create date
25/01/2008 14:00
Last modification date
20/08/2019 16:00
Usage data