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PMID: 9218505 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Role of nitric oxide in obesity-induced beta cell disease.

The Journal of clinical investigation ·Vol. 100 ·No. 2 ·1997-07-15 ·Pages 290-5

Shimabukuro M, Ohneda M, Lee Y, Unger RH

Abstract

Here we report that free fatty acid-induced suppression of insulin output in prediabetic Zucker diabetic fatty (ZDF) rats is mediated by NO. When normal islets were cultured in 2 mM FFA, NO production and basal insulin secretion increased slightly. In cultured prediabetic ZDF islets, FFA induced a fourfold greater rise in NO, upregulated mRNA of inducible nitric oxide synthase (iNOS), and reduced insulin output; both nicotinamide and aminoguanidine, which lower NO, prevented the FFA-mediated increase in iNOS mRNA, reduced NO, and minimized the loss of insulin secretion. In vivo nicotinamide or aminoguanidine treatment of prediabetic ZDF rats prevented the iNOS expression in islets and decreased beta cell dysfunction while blocking beta cell destruction and hyperglycemia. We conclude that NO-lowering agents prevent adipogenic diabetes in obese rats.

MeSH Terms
Animals Blood Glucose/metabolism Cells, Cultured Diabetes Mellitus/metabolism Diabetes Mellitus, Type 2/metabolism Fatty Acids, Nonesterified/blood,pharmacology Gene Expression Regulation/genetics Glucose Transporter Type 2 Guanidines/pharmacology Insulin/metabolism Insulin Secretion Islets of Langerhans/drug effects,metabolism Male Monosaccharide Transport Proteins/metabolism Niacinamide/pharmacology Nitric Oxide/metabolism,pharmacology Nitric Oxide Synthase/metabolism Obesity/metabolism Pancreas/cytology,drug effects,metabolism RNA, Messenger/metabolism Rats Rats, Wistar Rats, Zucker
Chemicals
Blood Glucose Fatty Acids, Nonesterified Glucose Transporter Type 2 Guanidines Insulin Monosaccharide Transport Proteins RNA, Messenger Niacinamide Nitric Oxide Nitric Oxide Synthase pimagedine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shimabukuro M
Center for Diabetes Research and Gifford Laboratories, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Ohneda M
Lee Y
Unger R H
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119534
Published
1997-07-15
Pages
290-5
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508191
Subset
IM
Grants
NIDDK NIH HHS · DK-02700-37 · United States
External Links
PubMed source DOI: 10.1172/JCI119534 PMC Full Text View journal details
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