Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes.

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.