Protection from nicotinamide inhibition of interleukin-1 beta-induced RIN cell nitric oxide formation is associated with induction of MnSOD enzyme activity

Endocrinology. 1996 Nov;137(11):4806-10. doi: 10.1210/endo.137.11.8895350.


We have studied the long-term effects of nicotinamide (NIC) on the synthesis of NO by insulin producing cells. NIC delays the formation of nitrite by interleukin (IL)-1 beta-(IL-1, 25 U/ml)-stimulated RINm5F cells, and previous exposure of cells to IL-1 for 15 h prevents this effect. The delay is associated with a lack of cytokine-induced inducible nitric oxide synthase (iNOS) enzyme activity in cell extracts. NIC (20 mM) inhibits NO synthase (NOS) activity in extracts from cells incubated with IL-1 for 6 h and 24 h, and oxyhemoglobin counteracts this inhibition. Hence, NIC could scavenge O2- and allow NO to inhibit the enzyme. The NO donor SIN-1 inhibits in a concentration-dependent manner iNOS activity, and the effect is potentiated by NIC. In intact cells, protection from NIC is associated with IL-1-induced expression of MnSOD activity, and reversible blockade of iNOS expression with pyrrolidine dithiocarbamate counteracts the NIC effect. We conclude that O2- plays a role in preventing NO inhibition of iNOS. The loss of this action coincides with the induction of MnSOD enzyme activity. In addition, the stimulation by NIC of IL-1-induced nitrite production in pyrrolidine dithiocarbamate-treated cells is a novel action that should be considered when the drug is proposed as potential agent for the prevention of insulin-dependent diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cell Line
  • Enzyme Induction / drug effects
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology
  • Niacinamide / pharmacology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / biosynthesis*
  • Pyrrolidines / pharmacology
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / pharmacology
  • Superoxide Dismutase / biosynthesis*
  • Superoxides / metabolism
  • Thiocarbamates / pharmacology
  • Time Factors
  • Vasodilator Agents / pharmacology


  • Antioxidants
  • Interleukin-1
  • Pyrrolidines
  • Recombinant Proteins
  • Thiocarbamates
  • Vasodilator Agents
  • Superoxides
  • pyrrolidine dithiocarbamic acid
  • Niacinamide
  • Nitric Oxide
  • linsidomine
  • Molsidomine
  • Nitric Oxide Synthase
  • Superoxide Dismutase