Jacob S, Dietze G J, Machicao F, Kuntz G, Augustin H J
Department of Internal Medicine, Stadtklinik, Baden-Baden, Germany.
Arzneimittelforschung. 1996 Mar;46(3):269-72.
Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Previous studies have shown that Actovegin, a hemodialysate of calf blood, which has been used for treatment of circulatory disorders for many years, improves glucose tolerance in NIDDM without affecting insulin levels; in vitro studies found an improvement of insulin-stimulated glucose uptake in adipocytes. This pilot study was initiated to see whether this compound augments insulin sensitivity after repeated treatment. Ten patients with NIDDM received the hemodialysate (Actovegin 2.000 pro infusions, 500 ml as daily infusions) over a period of 10 days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11; oral glucose tolerance test (oGTT) was done on day -4 and day 12. Parenteral administration of the hemodialysate markedly augmented insulin stimulated glucose disposal (glucose infusion rate and metabolic clearance rate) by more than 80% (p < 0.003 day 11 vs. day 0). Although tested 44 h after the last infusion, oGTT also improved significantly, as documented by the diminished area under the curve (AUC) for glucose, whereas the AUC for insulin remained unchanged. This is the first clinical study to show that parenteral administration of the tested hemodialysate results in a significant increase of insulin-stimulated glucose disposal in NIDDM. The exact mode of action of the hemodialysate in improving insulin sensitivity is currently not known. The hemodialysate possibly acts via a supplementation of inositol-phosphate-oligosaccharides (IPO), as in experimental studies IPOs isolated from the hemodialysate improved glucose uptake in adipocytes in an insulin-independent manner. Further studies are needed to elucidate the underlying mechanisms.
骨骼肌葡萄糖摄取的胰岛素抵抗是II型糖尿病（非胰岛素依赖型糖尿病）的一个显著特征；因此，药物干预应旨在提高胰岛素敏感性。先前的研究表明，爱维治（Actovegin），一种小牛血液的血液透析液，多年来一直用于治疗循环系统疾病，可改善非胰岛素依赖型糖尿病患者的糖耐量，而不影响胰岛素水平；体外研究发现它能改善脂肪细胞中胰岛素刺激的葡萄糖摄取。开展这项初步研究是为了观察这种化合物在重复治疗后是否能增强胰岛素敏感性。10名非胰岛素依赖型糖尿病患者在10天内接受了血液透析液（每次输注爱维治2000，每日输注500毫升）。在第0天和第11天进行了高胰岛素正常血糖葡萄糖钳夹试验；在第 -4天和第12天进行了口服葡萄糖耐量试验（oGTT）。静脉注射血液透析液显著增强了胰岛素刺激的葡萄糖处置（葡萄糖输注率和代谢清除率），增幅超过80%（第11天与第0天相比，p < 0.003）。尽管在最后一次输注后44小时进行测试，但oGTT也有显著改善，如葡萄糖曲线下面积（AUC）减小所示，而胰岛素的AUC保持不变。这是第一项表明静脉注射受试血液透析液可使非胰岛素依赖型糖尿病患者胰岛素刺激的葡萄糖处置显著增加的临床研究。目前尚不清楚血液透析液改善胰岛素敏感性的确切作用方式。血液透析液可能通过补充肌醇磷酸寡糖（IPO）起作用，因为在实验研究中，从血液透析液中分离出的IPO以胰岛素非依赖的方式改善了脂肪细胞中的葡萄糖摄取。需要进一步研究以阐明其潜在机制。
