Glucose stimulates the expression and activities of nitric oxide synthases in incubated rat islets: an effect counteracted by GLP-1 through the cyclic AMP/PKA pathway
Jimenez, Javier LU ; Lundquist, Ingmar LU and Salehi, S Albert LU
(2005)
In Cell and Tissue Research
319(2).
p.221-230
- Abstract
- We have examined the expression and activity of inducible nitric oxide synthase ( iNOS) and the activity of neuronal constitutive NOS ( ncNOS) in isolated rat pancreatic islets, stimulated by a "hyperglycaemic" concentration of glucose, and whether the NOS activities could be modulated by activation of the cyclic AMP/ protein kinase A ( cyclic AMP/PKA) system in relation to the insulin secretory process. Here, we show that glucose stimulation ( 20 mmol/l) induces iNOS and increases ncNOS activity. No iNOS is detectable at basal glucose levels (3.3 mmol/l). The addition of glucagon-like-peptide 1 (GLP-1) or dibutyryl-cAMP to islets incubated with 20 mmol/l glucose results in a marked suppression of iNOS expression and activity, a reduction... (More)
- We have examined the expression and activity of inducible nitric oxide synthase ( iNOS) and the activity of neuronal constitutive NOS ( ncNOS) in isolated rat pancreatic islets, stimulated by a "hyperglycaemic" concentration of glucose, and whether the NOS activities could be modulated by activation of the cyclic AMP/ protein kinase A ( cyclic AMP/PKA) system in relation to the insulin secretory process. Here, we show that glucose stimulation ( 20 mmol/l) induces iNOS and increases ncNOS activity. No iNOS is detectable at basal glucose levels (3.3 mmol/l). The addition of glucagon-like-peptide 1 (GLP-1) or dibutyryl-cAMP to islets incubated with 20 mmol/l glucose results in a marked suppression of iNOS expression and activity, a reduction in ncNOS activity and increased insulin release. The GLP-1-induced suppression of glucose-stimulated iNOS activity and expression and its stimulation of insulin release is, at least in part, PKA dependent, since the PKA inhibitor H-89 reverses the effects of GLP-1. These observations have been confirmed by confocal microscopy showing the glucose-stimulated expression of iNOS, its suppression by GLP-1 and its reversion by H-89 in beta-cells. We have also found that the NO scavenger cPTIO and the NOS inhibitor L-NAME potentiate the insulin response to glucose, again suggesting that NO is a negative modulator of glucose-stimulated insulin release. We conclude that the induction of iNOS and the increase in ncNOS activity caused by glucose in rat islets is suppressed by the cyclic AMP/ PKA system. The inhibition of iNOS expression by the GLP-1/ cyclic AMP/ PKA pathway might possibly be of therapeutic potential in NO-mediated beta-cell dysfunction and destruction. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/255407
- author
- Jimenez, Javier
LU
; Lundquist, Ingmar
LU
and Salehi, S Albert
LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- iNOS, cNOS, glucose toxicity, (male Sprague Dawley), rat, pancreatic islets, insulin secretion
- in
- Cell and Tissue Research
- volume
- 319
- issue
- 2
- pages
- 221 - 230
- publisher
- Springer
- external identifiers
-
- pmid:15558323
- wos:000226321600005
- scopus:12944303107
- ISSN
- 1432-0878
- DOI
- 10.1007/s00441-004-1013-4
- language
- English
- LU publication?
- yes
- id
- 84a8e10b-9caf-4919-b2ba-3dac05c21bf6 (old id 255407)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15558323&dopt=Abstract
- date added to LUP
- 2016-04-01 12:30:09
- date last changed
- 2022-01-27 05:59:44
@article{84a8e10b-9caf-4919-b2ba-3dac05c21bf6,
abstract = {{We have examined the expression and activity of inducible nitric oxide synthase ( iNOS) and the activity of neuronal constitutive NOS ( ncNOS) in isolated rat pancreatic islets, stimulated by a "hyperglycaemic" concentration of glucose, and whether the NOS activities could be modulated by activation of the cyclic AMP/ protein kinase A ( cyclic AMP/PKA) system in relation to the insulin secretory process. Here, we show that glucose stimulation ( 20 mmol/l) induces iNOS and increases ncNOS activity. No iNOS is detectable at basal glucose levels (3.3 mmol/l). The addition of glucagon-like-peptide 1 (GLP-1) or dibutyryl-cAMP to islets incubated with 20 mmol/l glucose results in a marked suppression of iNOS expression and activity, a reduction in ncNOS activity and increased insulin release. The GLP-1-induced suppression of glucose-stimulated iNOS activity and expression and its stimulation of insulin release is, at least in part, PKA dependent, since the PKA inhibitor H-89 reverses the effects of GLP-1. These observations have been confirmed by confocal microscopy showing the glucose-stimulated expression of iNOS, its suppression by GLP-1 and its reversion by H-89 in beta-cells. We have also found that the NO scavenger cPTIO and the NOS inhibitor L-NAME potentiate the insulin response to glucose, again suggesting that NO is a negative modulator of glucose-stimulated insulin release. We conclude that the induction of iNOS and the increase in ncNOS activity caused by glucose in rat islets is suppressed by the cyclic AMP/ PKA system. The inhibition of iNOS expression by the GLP-1/ cyclic AMP/ PKA pathway might possibly be of therapeutic potential in NO-mediated beta-cell dysfunction and destruction.}},
author = {{Jimenez, Javier and Lundquist, Ingmar and Salehi, S Albert}},
issn = {{1432-0878}},
keywords = {{iNOS; cNOS; glucose toxicity; (male Sprague Dawley); rat; pancreatic islets; insulin secretion}},
language = {{eng}},
number = {{2}},
pages = {{221--230}},
publisher = {{Springer}},
series = {{Cell and Tissue Research}},
title = {{Glucose stimulates the expression and activities of nitric oxide synthases in incubated rat islets: an effect counteracted by GLP-1 through the cyclic AMP/PKA pathway}},
url = {{http://dx.doi.org/10.1007/s00441-004-1013-4}},
doi = {{10.1007/s00441-004-1013-4}},
volume = {{319}},
year = {{2005}},
}