PMID- 22120830
OWN - NLM
STAT- MEDLINE
DCOM- 20120703
LR  - 20181217
IS  - 1873-1686 (Electronic)
IS  - 0167-0115 (Linking)
VI  - 174
IP  - 1-3
DP  - 2012 Feb 10
TI  - Nitric oxide (NO)--production and regulation of insulin secretion in islets of 
      freely fed and fasted mice.
PG  - 32-7
LID - 10.1016/j.regpep.2011.11.006 [doi]
AB  - 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 alpha-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.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Eckersten, Dag
AU  - Eckersten D
AD  - Department of Nephrology and Transplantation Skane University Hospital, Sweden.
FAU - Henningsson, Ragnar
AU  - Henningsson R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111124
PL  - Netherlands
TA  - Regul Pept
JT  - Regulatory peptides
JID - 8100479
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Keto Acids)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 816-66-0 (alpha-ketoisocaproic acid)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Arginine/pharmacology
MH  - Blood Glucose/analysis
MH  - Fasting/*metabolism
MH  - Female
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/enzymology/*metabolism
MH  - Keto Acids/pharmacology
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase/metabolism
EDAT- 2011/11/29 06:00
MHDA- 2012/07/04 06:00
CRDT- 2011/11/29 06:00
PHST- 2011/06/21 00:00 [received]
PHST- 2011/10/18 00:00 [revised]
PHST- 2011/11/10 00:00 [accepted]
PHST- 2011/11/29 06:00 [entrez]
PHST- 2011/11/29 06:00 [pubmed]
PHST- 2012/07/04 06:00 [medline]
AID - S0167-0115(11)00189-3 [pii]
AID - 10.1016/j.regpep.2011.11.006 [doi]
PST - ppublish
SO  - Regul Pept. 2012 Feb 10;174(1-3):32-7. doi: 10.1016/j.regpep.2011.11.006. Epub 
      2011 Nov 24.