Islet constitutive nitric oxide synthase and glucose regulation of insulin release in mice
Åkesson, Bengt LU ; Henningsson, Ragnar LU ; Salehi, S Albert LU
and Lundquist, Ingmar
LU
(1999)
In Journal of Endocrinology
163(1).
p.39-48
- Abstract
- We have studied, by a combined in vitro and in vivo approach, the relation between the inhibitory action of N(G)-nitro-l-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide synthase (NOS), on the activity of islet constitutive NOS (cNOS) and glucose regulation of islet hormone release in mice. The cNOS activity in islets incubated in vitro at 20 mM glucose was not appreciably affected by 0.05 or 0.5 mM L-NAME, but was greatly suppressed (-60%) by 5 mM L-NAME. Similarly, glucose-stimulated insulin release was unaffected by the lower concentrations of L-NAME but greatly enhanced in the presence of 5 mM of the NOS inhibitor. In incubated islets inhibition of cNOS activity resulted in a modestly enhanced insulin release in... (More)
- We have studied, by a combined in vitro and in vivo approach, the relation between the inhibitory action of N(G)-nitro-l-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide synthase (NOS), on the activity of islet constitutive NOS (cNOS) and glucose regulation of islet hormone release in mice. The cNOS activity in islets incubated in vitro at 20 mM glucose was not appreciably affected by 0.05 or 0.5 mM L-NAME, but was greatly suppressed (-60%) by 5 mM L-NAME. Similarly, glucose-stimulated insulin release was unaffected by the lower concentrations of L-NAME but greatly enhanced in the presence of 5 mM of the NOS inhibitor. In incubated islets inhibition of cNOS activity resulted in a modestly enhanced insulin release in the absence of glucose, did not display any effect at physiological or subphysiological glucose concentrations, but resulted in a markedly potentiated insulin release at hyperglycaemic glucose concentrations. In the absence of glucose, glucagon secretion was suppressed by L-NAME. The dynamics of glucose-induced insulin release and (45)Ca(2+) efflux from perifused islets revealed that L-NAME caused an immediate potentiation of insulin release, and a slight increase in (45)Ca(2+) efflux. In islets depolarized with 30 mM K(+) in the presence of the K(+)(ATP) channel opener, diazoxide, L-NAME still greatly potentiated glucose-induced insulin release. Finally, an i.v. injection of glucose to mice pretreated with L-NAME was followed by a markedly potentiated insulin response, and an improved glucose tolerance. In accordance, islets isolated directly ex vivo after L-NAME injection displayed a markedly reduced cNOS activity. In conclusion, we have shown here, for the first time, that biochemically verified suppression of islet cNOS activity, induced by the NOS inhibitor L-NAME, is accompanied by a marked potentiation of glucose-stimulated insulin release both in vitro and in vivo. The major action of NO to inhibit glucose-induced insulin release is probably not primarily linked to changes in Ca(2+) fluxes and is exerted mainly independently of membrane depolarization events. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1115107
- author
- Åkesson, Bengt
LU
; Henningsson, Ragnar
LU
; Salehi, S Albert
LU
and Lundquist, Ingmar
LU
- organization
- publishing date
- 1999
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Endocrinology
- volume
- 163
- issue
- 1
- pages
- 39 - 48
- publisher
- Society for Endocrinology
- external identifiers
-
- pmid:10495405
- scopus:0032885856
- ISSN
- 1479-6805
- DOI
- 10.1677/joe.0.1630039
- language
- English
- LU publication?
- yes
- id
- ed1892d7-c859-44bc-83ec-f1af576eeeb3 (old id 1115107)
- date added to LUP
- 2016-04-01 11:56:18
- date last changed
- 2022-03-13 02:50:25
@article{ed1892d7-c859-44bc-83ec-f1af576eeeb3,
abstract = {{We have studied, by a combined in vitro and in vivo approach, the relation between the inhibitory action of N(G)-nitro-l-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide synthase (NOS), on the activity of islet constitutive NOS (cNOS) and glucose regulation of islet hormone release in mice. The cNOS activity in islets incubated in vitro at 20 mM glucose was not appreciably affected by 0.05 or 0.5 mM L-NAME, but was greatly suppressed (-60%) by 5 mM L-NAME. Similarly, glucose-stimulated insulin release was unaffected by the lower concentrations of L-NAME but greatly enhanced in the presence of 5 mM of the NOS inhibitor. In incubated islets inhibition of cNOS activity resulted in a modestly enhanced insulin release in the absence of glucose, did not display any effect at physiological or subphysiological glucose concentrations, but resulted in a markedly potentiated insulin release at hyperglycaemic glucose concentrations. In the absence of glucose, glucagon secretion was suppressed by L-NAME. The dynamics of glucose-induced insulin release and (45)Ca(2+) efflux from perifused islets revealed that L-NAME caused an immediate potentiation of insulin release, and a slight increase in (45)Ca(2+) efflux. In islets depolarized with 30 mM K(+) in the presence of the K(+)(ATP) channel opener, diazoxide, L-NAME still greatly potentiated glucose-induced insulin release. Finally, an i.v. injection of glucose to mice pretreated with L-NAME was followed by a markedly potentiated insulin response, and an improved glucose tolerance. In accordance, islets isolated directly ex vivo after L-NAME injection displayed a markedly reduced cNOS activity. In conclusion, we have shown here, for the first time, that biochemically verified suppression of islet cNOS activity, induced by the NOS inhibitor L-NAME, is accompanied by a marked potentiation of glucose-stimulated insulin release both in vitro and in vivo. The major action of NO to inhibit glucose-induced insulin release is probably not primarily linked to changes in Ca(2+) fluxes and is exerted mainly independently of membrane depolarization events.}},
author = {{Åkesson, Bengt and Henningsson, Ragnar and Salehi, S Albert and Lundquist, Ingmar}},
issn = {{1479-6805}},
language = {{eng}},
number = {{1}},
pages = {{39--48}},
publisher = {{Society for Endocrinology}},
series = {{Journal of Endocrinology}},
title = {{Islet constitutive nitric oxide synthase and glucose regulation of insulin release in mice}},
url = {{http://dx.doi.org/10.1677/joe.0.1630039}},
doi = {{10.1677/joe.0.1630039}},
volume = {{163}},
year = {{1999}},
}