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Melatonin protects against streptozotocin, but not interleukin‐1β‐induced damage of rodent pancreatic β‐cells
Author(s) -
Andersson Annika K.,
Sandler Stellan
Publication year - 2001
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2001.300304.x
Subject(s) - melatonin , endocrinology , streptozotocin , medicine , pancreatic islets , islet , nitric oxide synthase , nitric oxide , nad+ kinase , biology , chemistry , insulin , diabetes mellitus , biochemistry , enzyme
In the present study, we examined whether melatonin can protect rodent pancreatic islets against streptozotocin (STZ) and interleukin‐1β (IL‐1β)‐induced suppression of β‐cell function. Formation of free radicals, DNA damage and extensive DNA repair leading to depletion of intracellular nicotinamide adenine dinucleotide (NAD) may mediate STZ toxicity. Activation of inducible nitric oxide synthase and nitric oxide (NO) formation may cause IL‐1β‐induced β‐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 μM–1 mM) 30 min prior to STZ (0.5 mM) or IL‐1β (25 U/mL) addition. After an additional 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‐1β experiments, islets were incubated for 48 hr with the cytokine before evaluation of islet function. We found that melatonin counteracted STZ‐induced inhibition of glucose metabolism and insulin release in cultured rat islets after 18 hr of recovery. Moreover, NAD levels were higher in the melatonin‐treated group at this time point. Melatonin had no effect on IL‐1β‐induced islet inhibition of glucose oxidation or NO formation. Diabetes induced by STZ (140 mg/kg body weight; i.v.) was effectively prevented by administration of melatonin (100 mg/kg body weight; i.p.) 30 min before STZ injection. We conclude that the protective effects of melatonin against β‐cell damage may be related to interference with DNA damage and poly(ADP‐ribose) polymerase (PARP) activation rather than through effects on NO generation pathways.