Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet NO generation in the mouse.
(2009) In Acta Physiologica 195(3). p.375-383- Abstract
- Aim: The role of islet nitric oxide (NO) production in insulin releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on beta-cell function might be related to perturbations of islet NO production. Methods: Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO-synthase (iNOS) with confocal microscopy. Results: RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol... (More)
- Aim: The role of islet nitric oxide (NO) production in insulin releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on beta-cell function might be related to perturbations of islet NO production. Methods: Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO-synthase (iNOS) with confocal microscopy. Results: RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose (20 mmol/l) displayed increased NO production derived from both neuronal constitutive NO-synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in beta-cells after incubation of islets at high but not low glucose. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose showed intense iNOS expression in beta-cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion: RX effectively counteracts the negative impact of beta-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS-inhibitory properties being of potential therapeutic value for treatment of beta-cell dysfunction in hyperglycaemia and type 2 diabetes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1243485
- author
- Meidute, Sandra LU ; Mosén, Henrik LU ; Lundquist, Ingmar LU and Salehi, S Albert LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- islet nitric oxide synthase isoenzymes, insulin release, imidazoline RX 871024, cholinergic stimulation, glucose stimulation
- in
- Acta Physiologica
- volume
- 195
- issue
- 3
- pages
- 375 - 383
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000262938900007
- pmid:18764864
- scopus:59149095001
- pmid:18764864
- ISSN
- 1748-1708
- DOI
- 10.1111/j.1748-1716.2008.01896.x
- language
- English
- LU publication?
- yes
- id
- 5d8adacb-e4c0-4bf2-9e8f-ca94b038b5ff (old id 1243485)
- alternative location
- http://www.ncbi.nlm.nih.gov/sites/entrez
- date added to LUP
- 2016-04-01 11:43:55
- date last changed
- 2022-01-26 17:23:16
@article{5d8adacb-e4c0-4bf2-9e8f-ca94b038b5ff, abstract = {{Aim: The role of islet nitric oxide (NO) production in insulin releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on beta-cell function might be related to perturbations of islet NO production. Methods: Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO-synthase (iNOS) with confocal microscopy. Results: RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose (20 mmol/l) displayed increased NO production derived from both neuronal constitutive NO-synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in beta-cells after incubation of islets at high but not low glucose. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose showed intense iNOS expression in beta-cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion: RX effectively counteracts the negative impact of beta-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS-inhibitory properties being of potential therapeutic value for treatment of beta-cell dysfunction in hyperglycaemia and type 2 diabetes.}}, author = {{Meidute, Sandra and Mosén, Henrik and Lundquist, Ingmar and Salehi, S Albert}}, issn = {{1748-1708}}, keywords = {{islet nitric oxide synthase isoenzymes; insulin release; imidazoline RX 871024; cholinergic stimulation; glucose stimulation}}, language = {{eng}}, number = {{3}}, pages = {{375--383}}, publisher = {{Wiley-Blackwell}}, series = {{Acta Physiologica}}, title = {{Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet NO generation in the mouse.}}, url = {{http://dx.doi.org/10.1111/j.1748-1716.2008.01896.x}}, doi = {{10.1111/j.1748-1716.2008.01896.x}}, volume = {{195}}, year = {{2009}}, }