Nakayama K, Murakami N, Ohta M, Kato K, Ida K, Mizota M, Miwa I, Okuda J
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan.
Eur J Pharmacol. 1995 Mar 24;276(1-2):77-83. doi: 10.1016/0014-2999(95)00015-d.
The effect of a single oral administration of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on serum glucose was investigated. In normal rats, M16209 (100 mg/kg) had a weak hypoglycemic effect but markedly stimulated the disappearance of serum glucose in intravenous glucose tolerance tests. In diabetic rats, M16209 (100 mg/kg) significantly suppressed the hyperglycemia of streptozotocin-induced, mildly diabetic rats and stimulated serum glucose disappearance in neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM) rats in glucose tolerance tests. Additionally, M16209 augmented insulin secretion in glucose-loaded, normal and NIDDM rats and restored the reduced serum insulin in streptozotocin-induced, mildly diabetic rats. M16209, however, showed no hypoglycemic effect in severely diabetic rats. In contrast, gliclazide, a sulfonylurea, showed a much more potent hypoglycemic effect in normal rats than in mildly diabetic rats. These results suggest that M16209 suppresses hypoglycemia through augmentation of glucose-stimulated insulin secretion. The antihyperglycemic activity of M16209, combined with its potent aldose reductase inhibiting activity, is expected to be beneficial in the treatment of diabetic complications.
研究了新型醛糖还原酶抑制剂M16209（1-（3-溴苯并[b]呋喃-2-基磺酰基）乙内酰脲）单次口服给药对血糖的影响。在正常大鼠中，M16209（100mg/kg）具有微弱的降血糖作用，但在静脉葡萄糖耐量试验中显著促进了血清葡萄糖的消失。在糖尿病大鼠中，M16209（100mg/kg）显著抑制链脲佐菌素诱导的轻度糖尿病大鼠的高血糖，并在葡萄糖耐量试验中促进新生链脲佐菌素诱导的非胰岛素依赖型糖尿病（NIDDM）大鼠血清葡萄糖的消失。此外，M16209增强了葡萄糖负荷的正常大鼠和NIDDM大鼠的胰岛素分泌，并恢复了链脲佐菌素诱导的轻度糖尿病大鼠降低的血清胰岛素水平。然而，M16209在重度糖尿病大鼠中未显示出降血糖作用。相比之下，磺脲类药物格列齐特在正常大鼠中显示出比轻度糖尿病大鼠更强的降血糖作用。这些结果表明，M16209通过增强葡萄糖刺激的胰岛素分泌来抑制低血糖。M16209的抗高血糖活性及其强大的醛糖还原酶抑制活性，有望在糖尿病并发症的治疗中发挥有益作用。
