Yusuf Muhammed, Kwong Huat Benny Tan, Hsu A, Whiteman Matthew, Bhatia Madhav, Moore Philip K
Department of Pharmacology, National University of Singapore, Block MD2, 18 Medical Drive, Singapore 117597, Singapore.
Biochem Biophys Res Commun. 2005 Aug 12;333(4):1146-52. doi: 10.1016/j.bbrc.2005.06.021.
This investigation is aimed to determine whether the biosynthesis of H(2)S, an endogenous vasodilator gas, is altered in the streptozotocin-diabetic rat. Plasma H(2)S concentration as well as the activity, and expression, of H(2)S synthesizing enzymes (namely cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthetase (CBS)) were measured in various tissues of non-diabetic, streptozotocin-diabetic and insulin-treated diabetic rats. H(2)S formation in pancreas and liver was increased in diabetic rats. Both CSE and CBS mRNAs were increased in liver of diabetic animals. Similarly, CBS mRNA was increased in pancreas. Insulin treatment restored the changes in H(2)S metabolism seen. The findings of this study suggest that the metabolism of H(2)S in pancreas and liver is altered in the streptozotocin-diabetic rat. This is the first study in which a derangement in H(2)S biosynthesis in diabetes has been demonstrated. H(2)S may play a part in the aetiology or development of diabetes in this animal model.
本研究旨在确定内源性血管舒张气体硫化氢（H₂S）的生物合成在链脲佐菌素诱导的糖尿病大鼠中是否发生改变。我们检测了非糖尿病大鼠、链脲佐菌素诱导的糖尿病大鼠以及胰岛素治疗的糖尿病大鼠不同组织中的血浆H₂S浓度，以及H₂S合成酶（即胱硫醚γ-裂解酶（CSE）和胱硫醚β-合成酶（CBS））的活性和表达。糖尿病大鼠胰腺和肝脏中的H₂S生成增加。糖尿病动物肝脏中CSE和CBS的mRNA均增加。同样，胰腺中CBS的mRNA也增加。胰岛素治疗使所观察到的H₂S代谢变化恢复正常。本研究结果表明，链脲佐菌素诱导的糖尿病大鼠胰腺和肝脏中H₂S的代谢发生了改变。这是首次证明糖尿病中H₂S生物合成紊乱的研究。在该动物模型中，H₂S可能在糖尿病的病因或发展中起作用。
