It is well-documented that melatonin influences insulin secretion. The effects are mediated by specific, high-affinity, pertussis-toxin-sensitive, G protein-coupled membrane receptors (MT(1) as well MT(2)), which are present in both the pancreatic tissue and islets of rats and humans, as well as in rat insulinoma cells (INS1). Via the Gi-protein-adenylatecyclase-3',5'-cyclic adenosine monophosphate (cAMP) and, possibly, the guanylatecyclase-cGMP pathways, melatonin decreases insulin secretion, whereas, by activating the Gq-protein-phospholipase C-IP(3) pathway, it has the opposite effect. For further analysis of the interactions between melatonin and insulin, diabetic rats were investigated with respect to melatonin synthesis in the pineal gland and plasma insulin levels. In this context, recent investigations have proven that type 2 diabetic rats and humans display decreased melatonin levels, whereas type 1 diabetic IDDM rats or those with diabetes induced by streptozotocin (STZ) of the present study show increased plasma melatonin levels and elevated AA-NAT-mRNA. Furthermore, the mRNA of pineal insulin receptors and beta1-adrenoceptors, including the clock genes Per1 and Bmal1 and the clock-controlled output gene Dbp, increases in both young and middle-aged STZ rats. The results therefore indicate that the decreased insulin levels in STZ-induced type 1 diabetes are associated with higher melatonin plasma levels. In good agreement with earlier investigations, it was shown that the elevated insulin levels observed in type 2 diabetes, are associated with decreased melatonin levels. The results thus prove that a melatonin-insulin antagonism exists. Astonishingly, notwithstanding the drastic metabolic disturbances in STZ-diabetic rats, the diurnal rhythms of the parameters investigated are maintained.

中文翻译：

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链脲佐菌素诱导的1型糖尿病大鼠松果体褪黑激素合成增加。

众所周知，褪黑激素会影响胰岛素分泌。这种作用是由高亲和力，对百日咳毒素敏感的G蛋白偶联膜受体（MT（1）和MT（2））介导的，该受体存在于大鼠和人类的胰腺组织和胰岛中，以及大鼠胰岛素瘤细胞（INS1）。褪黑素通过Gi蛋白-腺苷酸环化酶3'，5'-环腺苷一磷酸（cAMP）以及可能的鸟苷酸环化酶cGMP途径减少胰岛素分泌，而通过激活Gq蛋白磷脂酶C-IP（3 ）通路，其作用相反。为了进一步分析褪黑激素和胰岛素之间的相互作用，对糖尿病大鼠的松果体中褪黑激素合成和血浆胰岛素水平进行了研究。在这种情况下，最近的研究证明，本研究的2型糖尿病大鼠和人类的褪黑激素水平降低，而本研究的1型糖尿病IDDM大鼠或患有糖尿病的链脲佐菌素（STZ）诱导的糖尿病大鼠则显示血浆褪黑激素水平升高和AA-NAT-mRNA升高。此外，松果体胰岛素受体和β1-肾上腺素受体的mRNA，包括时钟基因Per1和Bmal1和时钟控制输出基因Dbp，在年轻和中年STZ大鼠中均增加。因此，结果表明，STZ诱导的1型糖尿病的胰岛素水平降低与褪黑激素血浆水平升高有关。与早期研究非常吻合，结果表明，在2型糖尿病中观察到的胰岛素水平升高与褪黑激素水平降低有关。因此，结果证明存在褪黑激素-胰岛素拮抗作用。令人惊讶的是，尽管在STZ糖尿病大鼠中发生了严重的代谢紊乱，所研究参数的昼夜节律仍然得以维持。