Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes.
Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes.
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DOI：
10.1038/srep10722
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发表时间：
2015-05-29
影响因子：
4.6
通讯作者：
Sekimizu K
中科院分区：
文献类型：
--
作者：
Matsumoto Y;Ishii M;Hayashi Y;Miyazaki S;Sugita T;Sumiya E;Sekimizu K
我们先前报道了家蚕血淋巴中的糖水平，即，在高葡萄糖饮食摄入后立即（1小时内）增加血液中的葡萄糖水平，给予人胰岛素可降低家蚕升高的血淋巴糖水平。然而，在该高血糖家蚕模型中，施用吡格列酮或二甲双胍（临床上用于治疗II型糖尿病的药物）没有效果。因此，在这里，我们建立了一个家蚕模型的II型糖尿病的抗糖尿病药物，如吡格列酮和二甲双胍的评价。高葡萄糖饲料喂养的家蚕在很长一段时间内（18小时）表现出高血糖表型。在这些高脂血症的蚕中，JNK（一种应激反应蛋白激酶）的磷酸化在脂肪体中增强，脂肪体是一种功能上类似于哺乳动物肝脏和脂肪组织的器官。从高脂血症蚕中分离的脂肪体表现出对人胰岛素的敏感性降低。高血糖蚕具有葡萄糖耐量受损，其特征在于高空腹血淋巴糖水平和在葡萄糖耐量试验中更高的血淋巴糖水平。吡格列酮或二甲双胍可改善高血糖蚕的糖耐量。这些结果表明，高血糖症的家蚕是有用的，用于评价候选药物的降血糖活性，对II型糖尿病。
We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1 h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18 h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.
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影响因子：
4.9
作者：
Hamamoto, H;Kurokawa, K;Sekimizu, K
通讯作者：
Sekimizu, K
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64.5
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Hirabayashi, Susumu;Baranski, Thomas J.;Cagan, Ross L.
通讯作者：
Cagan, Ross L.
影响因子：
3.7
作者：
Colca JR;McDonald WG;Cavey GS;Cole SL;Holewa DD;Brightwell-Conrad AS;Wolfe CL;Wheeler JS;Coulter KR;Kilkuskie PM;Gracheva E;Korshunova Y;Trusgnich M;Karr R;Wiley SE;Divakaruni AS;Murphy AN;Vigueira PA;Finck BN;Kletzien RF
通讯作者：
Kletzien RF