Development of a Novel Zebrafish Model for Type 2 Diabetes Mellitus

[Speaker] Liqing Zang:1
[Co-author] Yasuhito Shimada:2,3, Norihiro Nishimura:1
1:Graduate School of Regional Innovation Studies, Mie University, Japan, 2:Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Japan, 3:Department of Bioinformatics, Mie University Life Science Research Center, Japan

The world wide increase in type 2 diabetes mellitus (T2DM) makes it one of the major public health issue and economic implications. T2DM is a complex disorder resulted from the interaction between a genetic predisposition and behavioral and environmental risk factors. Recently, considerable emphasis has been placed on the early onset of T2DM and obesity. Although many high-fat diet-induced rodent models of obesity and diabetes exist, the zebrafish model for T2DM has not been established yet. To that end, we sought to develop and validate a zebrafish model of T2DM based on diet induced obesity (DIO). The DIO zebrafish showed significantly increased fasting blood glucose level, compared to normal-fed zebrafish. Intraperitoneal and oral glucose tolerance tests showed impaired glucose tolerance by overfeeding. Insulin production, which was determined indirectly by measuring the EGFP signal strength in overfed Tg(-1.0ins:EGFP)sc1 zebrafish, was increased in DIO zebrafish. The anti-diabetic drugs metformin and glimepiride ameliorated hyperglycemia in the overfed group, suggesting that this zebrafish can be used as a model of human T2DM. Finally, we conducted RNA deep sequencing and found that the gene expression profiling of liver-pancreas revealed pathways common to human T2DM. In summary, we developed a zebrafish model of T2DM that shows promise as a platform for mechanistic and therapeutic studies of diet-induced glucose intolerance and insulin resistance.

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