Advanced

Insulin feedback actions: complex effects involving isoforms of islet nitric oxide synthase.

Jimenez, Javier LU ; Lundquist, Ingmar LU ; Obermüller, Stefanie LU and Salehi, S Albert LU (2004) In Regulatory Peptides 122(2). p.109-118
Abstract
The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS).



The dose–response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05–0.1 nmol/l insulin stimulated, 1–100 nmol/l had no effect, whereas concentrations ≥250 nmol/l (“high insulin”), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3′-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin... (More)
The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS).



The dose–response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05–0.1 nmol/l insulin stimulated, 1–100 nmol/l had no effect, whereas concentrations ≥250 nmol/l (“high insulin”), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3′-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin (0.1 nmol/l). Moreover, high insulin markedly increased islet ncNOS activity and induced a strong iNOS activity. As shown biochemically and with confocal microscopy, the stimulatory action of high insulin on NOS activities and the associated inhibition of C-peptide release were reversed by raising cyclic AMP through addition of either glucagon-like peptide 1 (GLP-1) or dibutyryl cyclic AMP (Bt2cAMP) to the incubated islets.



We conclude that the positive feedback mechanisms of action of insulin are independent of islet NOS activities and remain unclear. The negative feedback action of insulin, however, can be explained by its ability to stimulate both islet ncNOS activity and the expression and activity of iNOS. The effects on iNOS are most likely transduced through phosphatidylinositol 3′-kinase and are counteracted by raising islet cyclic AMP levels. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Isoforms of islet nitric oxide synthase, Isolated islets, Insulin feedback, GLP-1, Cyclic AMP
in
Regulatory Peptides
volume
122
issue
2
pages
109 - 118
publisher
Elsevier
external identifiers
  • wos:000224332500008
  • scopus:4544383688
ISSN
1873-1686
DOI
10.1016/j.regpep.2004.06.004
language
English
LU publication?
yes
id
3c8821f7-b937-4771-9421-6f8f45026837 (old id 127286)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15380928&dopt=Abstract
date added to LUP
2007-07-13 15:45:02
date last changed
2017-09-17 05:36:48
@article{3c8821f7-b937-4771-9421-6f8f45026837,
  abstract     = {The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS).<br/><br>
<br/><br>
The dose–response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05–0.1 nmol/l insulin stimulated, 1–100 nmol/l had no effect, whereas concentrations ≥250 nmol/l (“high insulin”), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3′-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin (0.1 nmol/l). Moreover, high insulin markedly increased islet ncNOS activity and induced a strong iNOS activity. As shown biochemically and with confocal microscopy, the stimulatory action of high insulin on NOS activities and the associated inhibition of C-peptide release were reversed by raising cyclic AMP through addition of either glucagon-like peptide 1 (GLP-1) or dibutyryl cyclic AMP (Bt2cAMP) to the incubated islets.<br/><br>
<br/><br>
We conclude that the positive feedback mechanisms of action of insulin are independent of islet NOS activities and remain unclear. The negative feedback action of insulin, however, can be explained by its ability to stimulate both islet ncNOS activity and the expression and activity of iNOS. The effects on iNOS are most likely transduced through phosphatidylinositol 3′-kinase and are counteracted by raising islet cyclic AMP levels.},
  author       = {Jimenez, Javier and Lundquist, Ingmar and Obermüller, Stefanie and Salehi, S Albert},
  issn         = {1873-1686},
  keyword      = {Isoforms of islet nitric oxide synthase,Isolated islets,Insulin feedback,GLP-1,Cyclic AMP},
  language     = {eng},
  number       = {2},
  pages        = {109--118},
  publisher    = {Elsevier},
  series       = {Regulatory Peptides},
  title        = {Insulin feedback actions: complex effects involving isoforms of islet nitric oxide synthase.},
  url          = {http://dx.doi.org/10.1016/j.regpep.2004.06.004},
  volume       = {122},
  year         = {2004},
}