Tamakawa H, Miyata A, Satoh K, Miyake Y, Matsuo H, Arimura A, Kangawa K
National Cardiovascular Center Research Institute, Suita-city, Osaka, Japan.
Peptides. 1998;19(9):1497-502. doi: 10.1016/s0196-9781(98)00107-7.
Pituitary adenylate cyclase activating polypeptide (PACAP), which was isolated from ovine hypothalamic extract, has been shown to have a physiological role in the regulation of insulin or islet functions. In streptozotocin (STZ)-induced diabetic rats, we examined the content of PACAP immunoreactivity and gene expression of three specific receptors. Four weeks after administration of STZ (50 mg/kg), plasma glucose levels increased 3.3-fold, and plasma insulin levels decreased to one-tenth as compared with the control. The content of PACAP immunoreactivity in the pancreas potently increased by 30%, but the content of vasoactive intestinal polypeptide (VIP) immunoreactivity was not changed. In the other tissues, the content of PACAP immunoreactivity did not significantly change except in the hypothalamus, which showed a 10% increment. In the expression level of PACAP/VIP receptors, semi-quantitative RT-PCR analysis revealed that VIP1/PACAP receptor mRNA significantly increased as compared with the other two types of receptors in the pancreas of STZ-induced diabetic rats. These findings suggest that PACAP and VIP1/PACAP receptor might be involved in the pathophysiology of diabetes mellitus.
垂体腺苷酸环化酶激活多肽（PACAP）是从羊下丘脑提取物中分离出来的，已被证明在胰岛素或胰岛功能的调节中具有生理作用。在链脲佐菌素（STZ）诱导的糖尿病大鼠中，我们检测了PACAP免疫反应性的含量以及三种特异性受体的基因表达。给予STZ（50mg/kg）四周后，与对照组相比，血浆葡萄糖水平增加了3.3倍，血浆胰岛素水平降至十分之一。胰腺中PACAP免疫反应性的含量显著增加了30%，但血管活性肠肽（VIP）免疫反应性的含量没有变化。在其他组织中，除下丘脑显示增加10%外，PACAP免疫反应性的含量没有显著变化。在PACAP/VIP受体的表达水平上，半定量逆转录-聚合酶链反应（RT-PCR）分析显示，与STZ诱导的糖尿病大鼠胰腺中的其他两种受体相比，VIP1/PACAP受体mRNA显著增加。这些发现表明，PACAP和VIP1/PACAP受体可能参与了糖尿病的病理生理过程。
