Animal Experimentation system as an infrastructure to support translational progression of diabetes research to medical practice

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The aim of this project is to establish an animal experimentation system expecting to progress translational research for type 2 diabetes disease. Type 2 diabetes considers as one of multiple risk factors for other lifestyle-related] diseases, and many factors influence for the disease such as genetic and environmental contribution. Therefore, we set up genetic background with strict congenic conditions. Knockout (KO) mice for IRS1 gene and IRS2 gene were bred into C57BU6 (B6) strain respectively. We also bred with 129 strains for those gene knockdown mice. The earlier onset of diabetic symptoms such as hyper blood glucose levels, intolerance in GTT (glucose tolerance test) and resistance in'Tr (insulin tolerant test) were observed in B6-IRS2 KO than original hybrid strain. B6-IRS2 KO mice caused diabetic in six weeks of age. There were any obvious phenotypic difference observed between mice delivered by natural mating and those by using in vitro fertilization and embryo transfer technology. B6-IRS2 KO mice were fed three types of foods containing with 5%, 10% and 15% of fat, respectively. Progression of the disease was observed on GTT in the group with 10% fat, and both on GTT and ITT in the 15% fat-feeding group. Clinical value of GTT was getting worse in 129-IRS2 KO mice than those of B6 background. On the other hand, 129-IRS2 KO mice showed relatively good response against insulin treatment.