Adrenoceptor Expression and Diurnal Rhythms of Melatonin and Its Precursors in the Pineal Gland of Type 2 Diabetic Goto-Kakizaki Rats
Adrenoceptor Expression and Diurnal Rhythms of Melatonin and Its Precursors in the Pineal Gland of Type 2 Diabetic Goto-Kakizaki Rats
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DOI：
10.1210/en.2009-1299
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发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Peschke, Elmar
中科院分区：
文献类型：
--
作者：
Bach, Andreas Gunter;Muehlbauer, Eckhard;Peschke, Elmar
松果体褪黑激素夜间释放的减少与动物和人类的衰老和慢性疾病有关。褪黑激素在2型糖尿病中具有保护作用;然而，它的合成本身在疾病中受到影响。本研究旨在检测2型糖尿病Goto-Kakizaki（GK）大鼠松果体褪黑激素合成的关键受损步骤。因此，血浆褪黑激素浓度和褪黑激素及其前体（色氨酸，5-羟基色氨酸，血清素，和N-乙酰血清素）的松果体含量进行了定量比较，与Wistar大鼠（每组8和50周龄）在一个昼夜的方式（每组四只动物，每个时间点）在GK大鼠。此外，松果体肾上腺素受体亚型mRNA的表达进行了研究。我们发现，在糖尿病GK大鼠中，1）抑制性α-2-肾上腺素受体的表达明显强于Wistar大鼠，2）5-羟色氨酸的形成严重受损，3）松果体蛋白质含量明显减少，与Wistar大鼠相比。这是第一次在2型糖尿病大鼠模型中以昼夜方式检查褪黑激素合成。本数据揭示了糖尿病动物褪黑激素分泌减少的几个原因，并提出了褪黑激素和胰岛素之间相互作用的重要联系。（内分泌学151：2483-2493，2010）
A decrease in the nighttime release of the pineal hormone melatonin is associated with aging and chronic diseases in animals an humans. Melatonin has a protective role in type 2 diabetes; however, its synthesis itself is affected in the disease. The aim of this study was to detect crucially impaired steps in the pineal melatonin synthesis of type 2 diabetic Goto-Kakizaki (GK) rats. Therefore, plasma melatonin concentrations and the pineal content of melatonin and its precursors (tryptophan, 5-hydroxytryptophan, serotonin, and N-acetylserotonin) were quantified in GK rats compared with Wistar rats (each group 8 and 50 wk old) in a diurnal manner (four animals per group and per time point). Additionally, the expression of pineal adrenoceptor subtype mRNA was investigated. We found that in diabetic GK rats, 1) inhibitory alpha-2-adrenoceptors are significantly more strongly expressed than in Wistar rats, 2) the formation of 5-hydroxytryptophan is crucially impaired, and 3) the pineal gland protein content is significantly reduced compared with that in Wistar rats. This is the first time that melatonin synthesis is examined in a type 2 diabetic rat model in a diurnal manner. The present data unveil several reasons for a reduced melatonin secretion in diabetic animals and present an important link in the interaction between melatonin and insulin. (Endocrinology 151: 2483-2493, 2010)