Role of nitric oxide in obesity-induced β cell disease

Michio Shimabukuro, Makoto Ohneda, Young H Lee, Roger H Unger

Research output: Contribution to journalArticle

239 Citations (Scopus)

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 β cell dysfunction while blocking β cell destruction and hyperglycemia. We conclude that NO-lowering agents prevent adipogenic diabetes in obese rats.

Original languageEnglish (US)
Pages (from-to)290-295
Number of pages6
JournalJournal of Clinical Investigation
Volume100
Issue number2
StatePublished - Jul 15 1997

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Nitric Oxide
Nitric Oxide Synthase Type II
Obesity
Insulin
Niacinamide
Messenger RNA
Islets of Langerhans
Nonesterified Fatty Acids
Hyperglycemia
pimagedine

Keywords

  • Diabetes
  • Inducible nitric oxide synthase
  • Nitric oxide
  • Obesity
  • Zucker diabetic fatty rat

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Role of nitric oxide in obesity-induced β cell disease. / Shimabukuro, Michio; Ohneda, Makoto; Lee, Young H; Unger, Roger H.

In: Journal of Clinical Investigation, Vol. 100, No. 2, 15.07.1997, p. 290-295.

Research output: Contribution to journalArticle

Shimabukuro, Michio ; Ohneda, Makoto ; Lee, Young H ; Unger, Roger H. / Role of nitric oxide in obesity-induced β cell disease. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 2. pp. 290-295.
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