Ramachandran B, Kandaswamy M, Narayanan V, Subramanian S
Department of Biochemistry and Molecular Biology, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.
Diabetes Obes Metab. 2003 Nov;5(6):455-61. doi: 10.1046/j.1463-1326.2003.00302.x.
The vanadium complexes so far tested for their insulin mimetic effects are either mono- or binuclear and contain only acyclic ligands. The leaching or hydrolysis of vanadyl ions from these complexes is much easier, and hence they elicit side effects. In the present study, a new binuclear macrocyclic oxovanadium complex was synthesized, and its efficacy was studied on streptozotocin (STZ)-induced diabetic rats over a period of 30 days.
The insulin mimetic effect of the complex was tested on the blood sugar level in the STZ-diabetic rats and on the activities of the carbohydrate-metabolizing enzymes present in the liver.
Administration of vanadium complex to STZ-induced diabetic rats decreased blood glucose levels from hyperglycaemic to normoglycaemic when compared to diabetic rats. The activity of carbohydrate-metabolizing enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen content were increased to near normal in vanadium complex-administered diabetic rats. The biochemical studies such as assay of blood urea and glutamate oxaloacetate transaminases revealed that the complex is not toxic to the system.
The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact macrocyclic form. Further, the vanadyl ions present in the macrocyclic binuclear oxovanadium complex are very close to each other, and this may enhance the insulin mimetic activity by synergic effect.
迄今为止,为测试其胰岛素模拟作用而研究的钒配合物均为单核或双核,且仅含有无环配体。这些配合物中钒离子的浸出或水解要容易得多,因此会引发副作用。在本研究中,合成了一种新型双核大环氧钒配合物,并在30天的时间内研究了其对链脲佐菌素(STZ)诱导的糖尿病大鼠的疗效。
在STZ诱导的糖尿病大鼠的血糖水平以及肝脏中存在的碳水化合物代谢酶的活性上测试该配合物的胰岛素模拟作用。
与糖尿病大鼠相比,给STZ诱导的糖尿病大鼠施用钒配合物可使血糖水平从高血糖降至正常血糖。在施用钒配合物的糖尿病大鼠中,己糖激酶、葡萄糖-6-磷酸脱氢酶、糖原合酶等碳水化合物代谢酶的活性以及糖原含量增加至接近正常水平。血尿素和谷氨酸草酰乙酸转氨酶测定等生化研究表明该配合物对该系统无毒。
该配合物的无毒性质可能归因于完整大环形式的钒离子的存在。此外,大环双核氧钒配合物中存在的钒离子彼此非常接近,这可能通过协同作用增强胰岛素模拟活性。