Development of a Novel Zebrafish Model for Type 2 Diabetes Mellitus

• Main Authors: Liqing Zang, Yasuhito Shimada, Norihiro Nishimura
• Format: Article
• Language: English
• Published: Nature Publishing Group 2017-05-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-017-01432-w

Abstract Obesity is a major cause of type 2 diabetes mellitus (T2DM) in mammals. We have previously established a zebrafish model of diet-induced obesity (DIO zebrafish) by overfeeding Artemia. Here we created DIO zebrafish using a different method to induce T2DM. Zebrafish were overfed a commercially available fish food using an automated feeding system. We monitored the fasting blood glucose levels in the normal-fed group (one feed/day) and overfed group (six feeds/day) over an 8-week period. The fasting blood glucose level was significantly increased in DIO zebrafish compared with that of 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 hyperglycaemia 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.