Islet function phenotype in gastrin-releasing Peptide receptor gene-deficient mice.
(2002) In Endocrinology 143(10). p.3717-3726- Abstract
- Gastrin-releasing peptide (GRP) is an islet neuropeptide that stimulates insulin secretion. To explore whether islet GRP contributes to neurally mediated insulin secretion, we studied GRP receptor (GRPR)-deleted mice. By using RT-PCR we showed that GRPR mRNA is expressed in islets of wild-type mice, but is lost in GRPR-deleted mice. Functional studies revealed that GRP potentiates glucose-stimulated insulin secretion in wild-type animals, but not in GRPR-deleted mice. This shows that GRPR is the receptor subtype mediating GRP-induced insulin secretion and that GRPR-deleted mice are tools for studying the physiological role of islet GRP. We found that GRPR-deleted mice display 1) augmentation of the insulin response to glucose by a... (More)
- Gastrin-releasing peptide (GRP) is an islet neuropeptide that stimulates insulin secretion. To explore whether islet GRP contributes to neurally mediated insulin secretion, we studied GRP receptor (GRPR)-deleted mice. By using RT-PCR we showed that GRPR mRNA is expressed in islets of wild-type mice, but is lost in GRPR-deleted mice. Functional studies revealed that GRP potentiates glucose-stimulated insulin secretion in wild-type animals, but not in GRPR-deleted mice. This shows that GRPR is the receptor subtype mediating GRP-induced insulin secretion and that GRPR-deleted mice are tools for studying the physiological role of islet GRP. We found that GRPR-deleted mice display 1) augmentation of the insulin response to glucose by a mechanism inhibited by ganglionic blockade; 2) increased insulin responsiveness also to the cholinergic agonist carbachol, but not to arginine; 3) impaired insulin and glucagon responses to autonomic nerve activation by 2-deoxyglucose; 4) normal islet adaptation to high fat-induced insulin resistance and fasting; and 5) normal islet cytoarchitecture, as revealed by immunocytochemistry of insulin and glucagon. In conclusion, 1) GRPR is the receptor subtype mediating the islet effects of GRP; 2) GRP contributes to insulin secretion induced by activation of the autonomic nerves; and 3) deletion of GRPR is compensated by increased cholinergic sensitivity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/110263
- author
- Persson, Kristin ; Pacini, Giovanni ; Sundler, Frank LU and Ahrén, Bo LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Endocrinology
- volume
- 143
- issue
- 10
- pages
- 3717 - 3726
- publisher
- Oxford University Press
- external identifiers
-
- pmid:12239081
- wos:000178212800003
- scopus:0036773332
- ISSN
- 0013-7227
- DOI
- 10.1210/en.2002-220371
- language
- English
- LU publication?
- yes
- id
- 05650dff-a93e-47e1-aa0d-925c39891ca0 (old id 110263)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12239081&dopt=Abstract
- date added to LUP
- 2016-04-01 11:52:02
- date last changed
- 2022-01-26 19:26:03
@article{05650dff-a93e-47e1-aa0d-925c39891ca0, abstract = {{Gastrin-releasing peptide (GRP) is an islet neuropeptide that stimulates insulin secretion. To explore whether islet GRP contributes to neurally mediated insulin secretion, we studied GRP receptor (GRPR)-deleted mice. By using RT-PCR we showed that GRPR mRNA is expressed in islets of wild-type mice, but is lost in GRPR-deleted mice. Functional studies revealed that GRP potentiates glucose-stimulated insulin secretion in wild-type animals, but not in GRPR-deleted mice. This shows that GRPR is the receptor subtype mediating GRP-induced insulin secretion and that GRPR-deleted mice are tools for studying the physiological role of islet GRP. We found that GRPR-deleted mice display 1) augmentation of the insulin response to glucose by a mechanism inhibited by ganglionic blockade; 2) increased insulin responsiveness also to the cholinergic agonist carbachol, but not to arginine; 3) impaired insulin and glucagon responses to autonomic nerve activation by 2-deoxyglucose; 4) normal islet adaptation to high fat-induced insulin resistance and fasting; and 5) normal islet cytoarchitecture, as revealed by immunocytochemistry of insulin and glucagon. In conclusion, 1) GRPR is the receptor subtype mediating the islet effects of GRP; 2) GRP contributes to insulin secretion induced by activation of the autonomic nerves; and 3) deletion of GRPR is compensated by increased cholinergic sensitivity.}}, author = {{Persson, Kristin and Pacini, Giovanni and Sundler, Frank and Ahrén, Bo}}, issn = {{0013-7227}}, language = {{eng}}, number = {{10}}, pages = {{3717--3726}}, publisher = {{Oxford University Press}}, series = {{Endocrinology}}, title = {{Islet function phenotype in gastrin-releasing Peptide receptor gene-deficient mice.}}, url = {{http://dx.doi.org/10.1210/en.2002-220371}}, doi = {{10.1210/en.2002-220371}}, volume = {{143}}, year = {{2002}}, }