Deparment of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, Granada, Spain.
J Pineal Res. 2012 Mar;52(2):203-10. doi: 10.1111/j.1600-079X.2011.00928.x. Epub 2011 Aug 25.
The aim of this study was to investigate the effects of melatonin on glucose homeostasis in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups, each composed of ten rats: naive (N), vehicle treated (V), and melatonin treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. ZDF rats developed DM (fasting hyperglycemia, 460±39.8mg/dL; HbA(1) c 8.3±0.5%) with both insulin resistance (HOMA-IR 9.28±0.9 versus 1.2±0.1 in ZL) and decreased β-cell function (HOMA1-%B) by 75%, compared with ZL rats. Melatonin reduced fasting hyperglycemia by 18.6% (P<0.05) and HbA(1) c by 11% (P<0.05) in ZDF rats. Also, melatonin lowered insulinemia by 15.9% (P<0.05) and HOMA-IR by 31% (P<0.01) and increased HOMA1-%B by 14.4% (P<0.05). In addition, melatonin decreased hyperleptinemia by 34% (P<0.001) and raised hypoadiponectinemia by 40% (P<0.001) in ZDF rats. Moreover, melatonin reduced serum free fatty acid levels by 13.5% (P<0.05). These data demonstrate that oral melatonin administration ameliorates glucose homeostasis in young ZDF rats by improving both insulin action and β-cell function. These observations have implications on melatonin's possible use as a new pharmacologic therapy for improving glucose homeostasis and of obesity-related T2DM, in young subjects.
本研究旨在探讨褪黑素对年轻雄性 Zucker 糖尿病肥胖（ZDF）大鼠葡萄糖稳态的影响，ZDF 大鼠是代谢综合征和 2 型糖尿病（T2DM）的实验模型。使用 ZDF 大鼠（n=30）和瘦型同窝对照（ZL）（n=30）。在 6 周龄时，将瘦型和肥胖型动物分为三组，每组由 10 只大鼠组成：未处理（N）、未处理对照（V）和褪黑素处理（M）（10mg/kg/天），持续 6 周。将褪黑素添加到饮用水中。ZDF 大鼠发生糖尿病（空腹高血糖，460±39.8mg/dL；HbA(1)c 8.3±0.5%），同时伴有胰岛素抵抗（HOMA-IR 9.28±0.9 与 ZL 中的 1.2±0.1 相比）和β细胞功能降低（HOMA1-%B 降低 75%）。褪黑素使 ZDF 大鼠的空腹血糖降低 18.6%（P<0.05），HbA(1)c 降低 11%（P<0.05）。此外，褪黑素使胰岛素血症降低 15.9%（P<0.05），HOMA-IR 降低 31%（P<0.01），HOMA1-%B 增加 14.4%（P<0.05）。此外，褪黑素使 ZDF 大鼠的高瘦素血症降低 34%（P<0.001），低脂联素血症增加 40%（P<0.001）。此外，褪黑素使血清游离脂肪酸水平降低 13.5%（P<0.05）。这些数据表明，口服褪黑素可通过改善胰岛素作用和β细胞功能来改善年轻 ZDF 大鼠的葡萄糖稳态。这些观察结果表明，褪黑素可能作为改善葡萄糖稳态和肥胖相关 T2DM 的新药物治疗方法，在年轻人群中具有应用前景。
