Advanced

Impaired glucose-stimulated insulin secretion in the GK rat is associated with abnormalities in islet nitric oxide production.

Mosén, Henrik LU ; Ostenson, Claes-Göran; Lundquist, Ingmar LU ; Alm, Per LU ; Henningsson, Ragnar; Jimenez, Javier LU ; Guenifi, Amel; Efendic, Suad and Salehi, S Albert LU (2008) In Regulatory Peptides 151. p.139-146
Abstract
We investigated implications of nitric oxide (NO) derived from islet neuronal constitutive NO synthase (ncNOS) and inducible NOS (iNOS) on insulin secretory mechanisms in the mildly diabetic GK rat. Islets from GK rats and Wistar controls were analysed for ncNOS and iNOS by HPLC, immunoblotting and immunocytochemistry in relation to insulin secretion stimulated by glucose or l-arginine in vitro and in vivo. No obvious difference in ncNOS fluorescence in GK vs control islets was seen but freshly isolated GK islets displayed a marked iNOS expression and activity. After incubation at low glucose GK islets showed an abnormal increase in both iNOS and ncNOS activities. At high glucose the impaired glucose-stimulated insulin release was... (More)
We investigated implications of nitric oxide (NO) derived from islet neuronal constitutive NO synthase (ncNOS) and inducible NOS (iNOS) on insulin secretory mechanisms in the mildly diabetic GK rat. Islets from GK rats and Wistar controls were analysed for ncNOS and iNOS by HPLC, immunoblotting and immunocytochemistry in relation to insulin secretion stimulated by glucose or l-arginine in vitro and in vivo. No obvious difference in ncNOS fluorescence in GK vs control islets was seen but freshly isolated GK islets displayed a marked iNOS expression and activity. After incubation at low glucose GK islets showed an abnormal increase in both iNOS and ncNOS activities. At high glucose the impaired glucose-stimulated insulin release was associated with an increased iNOS expression and activity and NOS inhibition dose-dependently amplified insulin secretion in both GK and control islets. This effect by NOS inhibition was also evident in depolarized islets at low glucose, where forskolin had a further amplifying effect in GK but not in control islets. NOS inhibition increased basal insulin release in perfused GK pancreata and amplified insulin release after glucose stimulation in both GK and control pancreata, almost abrogating the nadir separating first and second phase in controls. A defective insulin response to l-arginine was seen in GK rats in vitro and in vivo, being partially restored by NOS inhibition. The results suggest that increased islet NOS activities might contribute to the defective insulin response to glucose and l-arginine in the GK rat. Excessive iNOS expression and activity might be deleterious for the beta-cells over time. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Regulatory Peptides
volume
151
pages
139 - 146
publisher
Elsevier
external identifiers
  • wos:000261813500021
  • pmid:18662725
  • scopus:56349139928
ISSN
1873-1686
DOI
10.1016/j.regpep.2008.07.002
language
English
LU publication?
yes
id
4699f77d-65ab-432b-a35a-e7364d73a84a (old id 1180807)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18662725?dopt=Abstract
date added to LUP
2008-08-07 11:36:56
date last changed
2017-08-27 05:43:18
@article{4699f77d-65ab-432b-a35a-e7364d73a84a,
  abstract     = {We investigated implications of nitric oxide (NO) derived from islet neuronal constitutive NO synthase (ncNOS) and inducible NOS (iNOS) on insulin secretory mechanisms in the mildly diabetic GK rat. Islets from GK rats and Wistar controls were analysed for ncNOS and iNOS by HPLC, immunoblotting and immunocytochemistry in relation to insulin secretion stimulated by glucose or l-arginine in vitro and in vivo. No obvious difference in ncNOS fluorescence in GK vs control islets was seen but freshly isolated GK islets displayed a marked iNOS expression and activity. After incubation at low glucose GK islets showed an abnormal increase in both iNOS and ncNOS activities. At high glucose the impaired glucose-stimulated insulin release was associated with an increased iNOS expression and activity and NOS inhibition dose-dependently amplified insulin secretion in both GK and control islets. This effect by NOS inhibition was also evident in depolarized islets at low glucose, where forskolin had a further amplifying effect in GK but not in control islets. NOS inhibition increased basal insulin release in perfused GK pancreata and amplified insulin release after glucose stimulation in both GK and control pancreata, almost abrogating the nadir separating first and second phase in controls. A defective insulin response to l-arginine was seen in GK rats in vitro and in vivo, being partially restored by NOS inhibition. The results suggest that increased islet NOS activities might contribute to the defective insulin response to glucose and l-arginine in the GK rat. Excessive iNOS expression and activity might be deleterious for the beta-cells over time.},
  author       = {Mosén, Henrik and Ostenson, Claes-Göran and Lundquist, Ingmar and Alm, Per and Henningsson, Ragnar and Jimenez, Javier and Guenifi, Amel and Efendic, Suad and Salehi, S Albert},
  issn         = {1873-1686},
  language     = {eng},
  pages        = {139--146},
  publisher    = {Elsevier},
  series       = {Regulatory Peptides},
  title        = {Impaired glucose-stimulated insulin secretion in the GK rat is associated with abnormalities in islet nitric oxide production.},
  url          = {http://dx.doi.org/10.1016/j.regpep.2008.07.002},
  volume       = {151},
  year         = {2008},
}