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Selective induction of inducible nitric oxide synthase in pancreatic islet of rat after an intravenous glucose or intralipid challenge.

Ekelund, Mats LU ; Qader, Saleem LU ; Jimenez, Javier LU and Salehi, S Albert LU (2006) In Nutrition 22(2006 Apr 22). p.652-660
Abstract
Objective: Constant exposure of pancreatic islets to high levels of glucose or free fatty acids can lead to irreversible beta-cell dysfunction, a process referred to as glucotoxicity or lipotoxicity, respectively. In this context a role for nitric oxide generated by pancreatic islet has been suggested. The present investigation examined whether the route of glucose administration, i.e., given orally (OG) or infused intravenously (IVG), could have any effect on the expression and activity of inducible nitric oxide synthase (iNOS) in pancreatic islets. Methods: Rats were infused with glucose (50%) or Intralipid intravenously for 24 h or given glucose orally. A freely fed control group (FF) was also included. At 24 h rats were killed and... (More)
Objective: Constant exposure of pancreatic islets to high levels of glucose or free fatty acids can lead to irreversible beta-cell dysfunction, a process referred to as glucotoxicity or lipotoxicity, respectively. In this context a role for nitric oxide generated by pancreatic islet has been suggested. The present investigation examined whether the route of glucose administration, i.e., given orally (OG) or infused intravenously (IVG), could have any effect on the expression and activity of inducible nitric oxide synthase (iNOS) in pancreatic islets. Methods: Rats were infused with glucose (50%) or Intralipid intravenously for 24 h or given glucose orally. A freely fed control group (FF) was also included. At 24 h rats were killed and blood samples were drawn for analysis of plasma insulin, glucagon, and glucose. Pancreatic islets were harvested from each animal and investigated for the occurrence of iNOS by the use of confocal microscopy, western blot, and high-performance liquid chromatographic analysis. The effect of intravenously infused glucose was then compared with the effect of an intravenous infusion of Intralipid (IL). Results: Plasma insulin levels were markedly decreased after 24 h of infusion of glucose (IVG group) or Intralipid (IL group) compared with the FF or OG group. Plasma glucagon and glucose levels were markedly increased in the IVG group, whereas both parameters were decreased in the IL group. No significant differences in plasma insulin, glucagon, or glucose were found between the OG and FF groups. Immunocytochemical (confocal microscopy), western blot, and biochemical (high-performance liquid chromatographic) analyses showed that a sustained increase in plasma level of glucose or free fatty acids by an intravenous infusion of either nutrient for 24 h resulted in a marked expression and activity of iNOS in pancreatic islets. No sign of iNOS expression could, however, be detected in the islets of FF control or OG rats. Conclusion: The data suggest that impaired beta-cell function found after 24 It of an intravenous infusion of glucose or Intralipid might be mediated, at least in part, by the induction of iNOS in pancreatic islets. This may subsequently result in an exclusive production of nitric oxide, which is deleterious for beta-cells. (C) 2006 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pancreatic islets, insulin secretion, glucose challenge, inducible nitric oxide synthase
in
Nutrition
volume
22
issue
2006 Apr 22
pages
652 - 660
publisher
Elsevier
external identifiers
  • pmid:16635563
  • wos:000237842500010
  • scopus:33646398356
ISSN
1873-1244
DOI
10.1016/j.nut.2006.01.006
language
English
LU publication?
yes
id
b093d708-bf38-4955-b188-194e219d6d0d (old id 155773)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16635563&dopt=Abstract
date added to LUP
2016-04-01 12:37:22
date last changed
2020-03-11 03:03:07
@article{b093d708-bf38-4955-b188-194e219d6d0d,
  abstract     = {Objective: Constant exposure of pancreatic islets to high levels of glucose or free fatty acids can lead to irreversible beta-cell dysfunction, a process referred to as glucotoxicity or lipotoxicity, respectively. In this context a role for nitric oxide generated by pancreatic islet has been suggested. The present investigation examined whether the route of glucose administration, i.e., given orally (OG) or infused intravenously (IVG), could have any effect on the expression and activity of inducible nitric oxide synthase (iNOS) in pancreatic islets. Methods: Rats were infused with glucose (50%) or Intralipid intravenously for 24 h or given glucose orally. A freely fed control group (FF) was also included. At 24 h rats were killed and blood samples were drawn for analysis of plasma insulin, glucagon, and glucose. Pancreatic islets were harvested from each animal and investigated for the occurrence of iNOS by the use of confocal microscopy, western blot, and high-performance liquid chromatographic analysis. The effect of intravenously infused glucose was then compared with the effect of an intravenous infusion of Intralipid (IL). Results: Plasma insulin levels were markedly decreased after 24 h of infusion of glucose (IVG group) or Intralipid (IL group) compared with the FF or OG group. Plasma glucagon and glucose levels were markedly increased in the IVG group, whereas both parameters were decreased in the IL group. No significant differences in plasma insulin, glucagon, or glucose were found between the OG and FF groups. Immunocytochemical (confocal microscopy), western blot, and biochemical (high-performance liquid chromatographic) analyses showed that a sustained increase in plasma level of glucose or free fatty acids by an intravenous infusion of either nutrient for 24 h resulted in a marked expression and activity of iNOS in pancreatic islets. No sign of iNOS expression could, however, be detected in the islets of FF control or OG rats. Conclusion: The data suggest that impaired beta-cell function found after 24 It of an intravenous infusion of glucose or Intralipid might be mediated, at least in part, by the induction of iNOS in pancreatic islets. This may subsequently result in an exclusive production of nitric oxide, which is deleterious for beta-cells. (C) 2006 Elsevier Inc. All rights reserved.},
  author       = {Ekelund, Mats and Qader, Saleem and Jimenez, Javier and Salehi, S Albert},
  issn         = {1873-1244},
  language     = {eng},
  number       = {2006 Apr 22},
  pages        = {652--660},
  publisher    = {Elsevier},
  series       = {Nutrition},
  title        = {Selective induction of inducible nitric oxide synthase in pancreatic islet of rat after an intravenous glucose or intralipid challenge.},
  url          = {http://dx.doi.org/10.1016/j.nut.2006.01.006},
  doi          = {10.1016/j.nut.2006.01.006},
  volume       = {22},
  year         = {2006},
}