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.
Highlights
The International Diabetes Federation reported that in 2013, more than 387 million people were living with diabetes and more than 90% of all diabetes cases were examples of type 2 diabetes mellitus (T2DM)[1]
To create diet-induced obesity (DIO) zebrafish with hyperglycaemia, we developed a new feeding method by overfeeding the fish with a commercial fish food, Otohime B2, using an automated feeding system
The quantity of diet fed to the overfed group (DIO) was six times that fed to the control group, providing 408 vs. 68 calories per fish per day, respectively
Summary
The International Diabetes Federation reported that in 2013, more than 387 million people were living with diabetes and more than 90% of all diabetes cases were examples of type 2 diabetes mellitus (T2DM)[1]. Thiazolidinediones (TZDs) bind to and activate PPARγ to improve insulin sensitivity[5]; and biguanides and TZDs act by directly or indirectly activating AMPK6, 7 These drugs are effective for the prevention of hyperglycaemia and diabetic complications such as cardiovascular disorders; they cannot repair pancreatic damage. We modified our overfeeding method by changing the fish food and using an automatic feeder We found that these new DIO zebrafish show higher blood glucose after a period of fasting (FBG) than normally-fed zebrafish. We further demonstrate this hyperglycaemic zebrafish to be a useful model for T2DM through glucose tolerance testing and measurements of insulin production and glycaemic response to human anti-diabetic drugs. A RNA-seq analysis of liver-pancreas tissues reveals that the T2DM zebrafish shares pathological pathways with humans
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