Melatonin protects against streptozotocin, but not interleukin-1 beta-induced damage of rodent pancreatic beta-cells

In the present study, we examined whether melatonin can protect rodent panc reatic islets against streptozotocin (STZ) and interleukin-1 beta (IL-1 bet a)-induced suppression of beta -cell function. Formation of free radicals, DNA damage and extensive DNA repair leading to depletion of intracellular n icotinamide adenine dinucleotide (NAD) may mediate STZ toxicity. Activation of inducible nitric oxide synthase and nitric oxide (NO) formation may cau se IL-1 beta -induced beta -cell impairment. We also studied the effect of melatonin against STZ-induced hyperglycemia in C57BL/Ks mice. For in vitro studies, cultured rat islets were exposed to melatonin (100 muM-1 mM) 30 mi n prior to STZ (0.5 mM) or IL-1 beta (25 U/mL) addition. After an additiona l 30 min incubation with STZ, islet function and NAD content were analyzed either acutely or after 18 hr of recovery in fresh culture medium. For IL-1 beta experiments, islets were incubated for 48 hr with the cytokine before evaluation of islet function. We found that melatonin counteracted STZ-ind uced inhibition of glucose metabolism and insulin release in cultured rat i slets after Is hr of recovery. Moreover, NAD levels were higher in the mela tonin-treated group at this time point. Melatonin had no effect on IL-lp-in duced islet inhibition of glucose oxidation or NO formation. Diabetes induc ed by STZ (140 mg/kg body weight; i.v.) was effectively prevented by admini stration of melatonin (100 mg/kg body weight; i.p.) 30 min before STZ injec tion. We conclude that the protective effects of melatonin against beta -ce ll damage may be related to interference with DNA damage and poly(ADP-ribos e) polymerase (PARP) activation rather than through effects on NO generatio n pathways.