Insulin-mimicking bioactivities of acylated inositol glycans in several mouse models of diabetes with or without obesity.
Insulin-mimicking bioactivities of acylated inositol glycans in several mouse models of diabetes with or without obesity.
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DOI：
10.1371/journal.pone.0100466
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
d'Alarcao M
中科院分区：
文献类型：
--
作者：
Suzuki S;Suzuki C;Hinokio Y;Ishigaki Y;Katagiri H;Kanzaki M;Azev VN;Chakraborty N;d'Alarcao M
推测低分子量的胰岛素模拟物质介导某些细胞内胰岛素作用。这些肌醇聚糖在胰岛素刺激时由糖基磷脂酰肌醇产生，可能控制多种胰岛素效应酶的活性。酰化肌醇聚糖（AIG）是通过GPI特异性磷脂酶C（GPI-PLC）和D（GPI-PLD）的作用切割无蛋白GPI前体而产生的。我们合成了AIGs（IG-1、IG-2、IG-13、IG-14和IG-15），然后评价了它们的胰岛素模拟生物活性。IG-1显著刺激3 T3-L1脂肪细胞和大鼠分离脂肪细胞的糖原合成和脂肪生成，并呈剂量依赖性。IG-2剂量依赖性地显著刺激大鼠分离的脂肪细胞中的脂肪生成。IG-15还增强3 T3-L1脂肪细胞中的糖原合成和脂肪生成。在正常饮食的C57 B6 N小鼠中，给予IG-1可降低血浆葡萄糖，增加肝脏和骨骼肌中的糖原含量，并改善葡萄糖耐量。IG-1的给药降低了STZ糖尿病C57 B6 N小鼠的血糖。IG-1可降低高脂饮食C57 B6 N小鼠和db/db小鼠的血糖，增加肝脏和骨骼肌中的糖原含量，并改善葡萄糖耐量。IG-1的长期治疗降低了高脂饮食的C57 B6 N小鼠和ob/ob小鼠的血糖，减少了食物摄入量和体重。因此，IG-1具有类似胰岛素的生物活性，并改善伴有或不伴有肥胖的糖尿病小鼠模型的葡萄糖耐量。
Insulin-mimetic species of low molecular weight are speculated to mediate some intracellular insulin actions. These inositol glycans, which are generated upon insulin stimulation from glycosylphosphatidylinositols, might control the activity of a multitude of insulin effector enzymes. Acylated inositol glycans (AIGs) are generated by cleavage of protein-free GPI precursors through the action of GPI-specific phospholipase C (GPI-PLC) and D (GPI-PLD). We synthesized AIGs (IG-1, IG-2, IG-13, IG-14, and IG-15) and then evaluated their insulin-mimicking bioactivities. IG-1 significantly stimulated glycogen synthesis and lipogenesis in 3T3-L1 adipocytes and rat isolated adipocytes dose-dependently. IG-2 significantly stimulated lipogenesis in rat isolated adipocytes dose-dependently. IG-15 also enhanced glycogen synthesis and lipogenesis in 3T3-L1 adipocytes. The administration of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with normal diets. The administration of IG-1 decreased plasma glucose in STZ-diabetic C57B6N mice. The treatment of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with high fat-diets and db/db mice. The long-term treatment of IG-1 decreased plasma glucose and reduced food intake and body weight in C57B6N mice with high fat-diets and ob/ob mice. Thus, IG-1 has insulin-mimicking bioactivities and improves glucose tolerance in mice models of diabetes with or without obesity.
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影响因子：
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通讯作者：
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