Nicotinamide prevents interleukin-1 effects on accumulated insulin release and nitric oxide production in rat islets of Langerhans.
Nicotinamide (NA) prevents macrophage- and interleukin-1 (IL-1)-mediated beta-cell damage in vitro as well as diabetes development in animal models of insulin-dependent diabetes mellitus (IDDM). IL-1 beta-mediated inhibition of insulin release and damage to beta-cells are associated with intracellular production of nitric oxide (NO) radicals. Therefore, we studied whether NA prevented IL-1 beta-induced islet NO production, measured as nitrite release from isolated rat islets, and, if so, whether this action was associated with prevention of IL-1 beta-mediated inhibition of insulin release. NA dose- and time-dependently inhibited and delayed IL-1 beta-induced islet NO production. Light microscopy detected that 25 mM of NA protected against IL-1 beta-induced islet damage. Five to 50 mM of NA dose-dependently reduced inhibition of accumulated islet insulin release induced by 150 pg/ml of IL-1 beta. NA was not able to reverse the reduced ability of IL-1 beta-treated islets to respond to an acute glucose challenge. NO or nitrite did not interact directly with NA, because NA did not reduce sodium nitroprusside-generated nitrite. No-synthase inhibition with L-arginine depletion abolished NO production but only partially reduced IL-1 beta-induced inhibition of accumulated insulin release. Complete inhibition of IL-1 beta effects could not be obtained by adding L-arginine analogues to L-arginine-depleted medium, indicating that an NO-independent action of IL-1 beta on islet insulin release may exist.(ABSTRACT TRUNCATED AT 250 WORDS)
Andersen
H U
HU
Steno Diabetes Center, Gentofte, Denmark.
Jørgensen
K H
KH
Egeberg
J
J
Mandrup-Poulsen
T
T
Nerup
J
J
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D009536:Niacinamide / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013997:Time Factors
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D009536:Niacinamide; D009569:Nitric Oxide; D001120:Arginine