Advanced

Nitric oxide (NO) - Production and regulation of insulin secretion in islets of freely fed and fasted mice

Eckersten, Dag LU and Henningsson, Ragnar LU (2012) In Regulatory Peptides 174(1-3). p.32-37
Abstract

Production of nitric oxide through the action of nitric oxide synthase (NOS) has been detected in the islets of Langerhans. The inducible isoform of NOS (iNOS) is induced by cytokines and might contribute to the development of type-1 diabetes, while the constitutive isoform (cNOS) is thought to be implicated in the physiological regulation of insulin secretion. In the present study we have detected and quantified islet cNOS- and iNOS-derived NO production concomitant with measuring its influence on insulin secretion in the presence of different secretagogues: glucose, l-arginine, l-leucine and α-ketoisocaproic acid (KIC) both during fasting and freely fed conditions. In intact islets from freely fed mice both cNOS- and iNOS-activity was... (More)

Production of nitric oxide through the action of nitric oxide synthase (NOS) has been detected in the islets of Langerhans. The inducible isoform of NOS (iNOS) is induced by cytokines and might contribute to the development of type-1 diabetes, while the constitutive isoform (cNOS) is thought to be implicated in the physiological regulation of insulin secretion. In the present study we have detected and quantified islet cNOS- and iNOS-derived NO production concomitant with measuring its influence on insulin secretion in the presence of different secretagogues: glucose, l-arginine, l-leucine and α-ketoisocaproic acid (KIC) both during fasting and freely fed conditions. In intact islets from freely fed mice both cNOS- and iNOS-activity was greatly increased by glucose (20. mmol/l). Fasting induced islet iNOS activity at both physiological (7. mmol/l) and high (20. mmol/l) glucose concentrations. NOS blockade increased insulin secretion both during freely fed conditions and after fasting. l-arginine stimulated islet cNOS activity and did not affect islet iNOS activity. l-leucine or KIC, known to enter the TCA cycle without affecting glycolysis, did not affect either islet cNOS- or iNOS activity. Accordingly, insulin secretion stimulated by l-leucine or KIC was unaffected by addition of l-NAME both during feeding and fasting. We conclude that both high glucose concentrations and fasting increase islet total NO production (mostly iNOS derived) which inhibit insulin secretion. The insulin secretagogues l-leucine and KIC, which do not affect glycolysis, do not interfere with the islet NO-NOS system.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Constitutive nitric oxide synthase (cNOS), Inducible nitric oxide synthase (iNOS), Insulin secretion, Nitric oxide (NO), TCA-cycle
in
Regulatory Peptides
volume
174
issue
1-3
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:84856461588
ISSN
0167-0115
DOI
10.1016/j.regpep.2011.11.006
language
English
LU publication?
no
id
1469e620-2ea9-4158-b8b1-6e7b05f0e4c1
date added to LUP
2019-06-28 09:46:03
date last changed
2019-11-17 05:00:52
@article{1469e620-2ea9-4158-b8b1-6e7b05f0e4c1,
  abstract     = {<p>Production of nitric oxide through the action of nitric oxide synthase (NOS) has been detected in the islets of Langerhans. The inducible isoform of NOS (iNOS) is induced by cytokines and might contribute to the development of type-1 diabetes, while the constitutive isoform (cNOS) is thought to be implicated in the physiological regulation of insulin secretion. In the present study we have detected and quantified islet cNOS- and iNOS-derived NO production concomitant with measuring its influence on insulin secretion in the presence of different secretagogues: glucose, l-arginine, l-leucine and α-ketoisocaproic acid (KIC) both during fasting and freely fed conditions. In intact islets from freely fed mice both cNOS- and iNOS-activity was greatly increased by glucose (20. mmol/l). Fasting induced islet iNOS activity at both physiological (7. mmol/l) and high (20. mmol/l) glucose concentrations. NOS blockade increased insulin secretion both during freely fed conditions and after fasting. l-arginine stimulated islet cNOS activity and did not affect islet iNOS activity. l-leucine or KIC, known to enter the TCA cycle without affecting glycolysis, did not affect either islet cNOS- or iNOS activity. Accordingly, insulin secretion stimulated by l-leucine or KIC was unaffected by addition of l-NAME both during feeding and fasting. We conclude that both high glucose concentrations and fasting increase islet total NO production (mostly iNOS derived) which inhibit insulin secretion. The insulin secretagogues l-leucine and KIC, which do not affect glycolysis, do not interfere with the islet NO-NOS system.</p>},
  author       = {Eckersten, Dag and Henningsson, Ragnar},
  issn         = {0167-0115},
  keyword      = {Constitutive nitric oxide synthase (cNOS),Inducible nitric oxide synthase (iNOS),Insulin secretion,Nitric oxide (NO),TCA-cycle},
  language     = {eng},
  month        = {02},
  number       = {1-3},
  pages        = {32--37},
  publisher    = {Elsevier},
  series       = {Regulatory Peptides},
  title        = {Nitric oxide (NO) - Production and regulation of insulin secretion in islets of freely fed and fasted mice},
  url          = {http://dx.doi.org/10.1016/j.regpep.2011.11.006},
  volume       = {174},
  year         = {2012},
}