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首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats
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Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

机译：磺酰脲类药物对大冢长岛德岛肥胖大鼠胰岛素抵抗的改善作用

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OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (KATP) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of KATP channels, insulin receptor β-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that KATP-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on KATP channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.
机译：OLETF（Otsuka Long-Evans Tokushima Fatty）大鼠的特征在于与肥胖相关的胰岛素抵抗，这是2型糖尿病的表型。磺酰脲类药物或苯甲酸衍生物作为ATP敏感性钾（K ATP ）通道的抑制剂可从市场上买到。本研究将磺酰脲类药物（格列美脲和格列齐特）与一种苯甲酸衍生物（瑞格列奈）相比，它们对改善OLETF大鼠的胰岛素敏感性具有长期影响。从29周龄开始溶解每种药物并用饮用水喂养。在45周龄时，在高葡萄糖负荷下，格列美脲治疗组的血糖恢复反应最大。在对肝，脂肪和骨骼肌组织中K ATP 通道的Kir6.2亚基，胰岛素受体β亚基以及2型和4型葡萄糖转运蛋白（GLUT）进行免疫组织化学分析后，磺酰脲类药物（格列美脲和格列齐特比repaglinide在OLETF大鼠中降低的表达恢复方面更有效。从这些结果来看，含有磺酰脲部分的K ATP 通道抑制剂似乎在降低胰岛素抵抗方面比具有苯甲酸部分的抑制剂更有效。与格列齐特相比，格列美脲对K ATP 通道抑制的非组织选择性可能进一步增强胰岛素敏感性的改善，除非考虑其他副作用。

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