Establishment Of A Diabetes Model And Effects Of Metformin On The Annual Fish Nothobranchius Guentheri

Background: Due to the bad living habits, the intake of high carbohydrate and high-fat diet, and the accelerated pace of life and lack of exercise and rest, the incidence of diabetes is increasing, and there is trend of getting younger. Diabetes can be divided into type 1 diabetes and type 2 diabetes, and both show elevated blood glucose levels. The increase of blood glucose leads to damages of blood vessels and nerves, liver, kidneys, eyes and other organs. Metformin, a commonly used non-insulin drug to treat diabetes, has a good curative effect to type 2 diabetes and has an effect of lossing weight. Compared to other diabetes drugs, the side effects of metformin is smaller, it rarely leads to lactic acidosis phenomenon. Nothobranchius guentheri is an annual tropical freshwater fish which lives mainly in Tanzania, East Africa. Now the annual fish is raising all over the world. It has the characteristics of short life cycle, high reproductive capacity and easy breeding, so it becomes a good experimental model organism. It is significant to construct a diabetes model for the research and treatment of diabetes, and the annual fish can be easily induced as a diabetic model of hyperglycemia.Objective: This article is intended to establish the Nothobranchius guentheri diabetes model to study the effect of metformin on the fish diabetes.Methods: 32 adult fish were randomly divided into two groups, the control group, the experimental group. The fish in experimental group were treated with 2% glucose solution immersing for one month and detected their level of blood glucose to determine if the diabetes model was constructed. 66 fish of 3-month-old were randomly divided into three groups, the control group, the group of high glucose and the group of metformin. There are 9 males and 11 females in each group. The fish in control group were reared in clean water, fed with ordinary food; the fish of high glucose were reared in a 2% aqueous solution of glucose, fed with ordinary food; thefish in high glucose and metformin group were reared similarly to the high glucose group, but fed food with metformin. The fish were treated for one month in each group. At the end of the experiment, the weight and body length, blood glucose,triglyceride and cholesterol levels were measured; SOD activity and MDA level were detected in each group. The histological changes of liver, kidney, the inner plexiform layer(IPL) and the inner nuclear layer(INL) of retina were observed.Results: 2% glucose solution immersing 3-month-old fish for one month induced a diabetes model using 16 annual fish Nothobranchius guentheri. The level of blood glucose was significantly increased in diabetes model group compared with the control group immersed in fresh water. The levels of blood glucose decreased while the fish soaked in high glucose solution and fed with metformin. The fish model with2% glucose treatment was characterized by significantly increased triglyceride cholesterol and MDA level, dercreased SOD activity. The high density lipoprotein didn’t significantly change in the diabetes model group compared with the control group. The high density lipoprotein extremely significantly decreased in the metformin group compared with the diabetes model group. The low density lipoprotein decreased in the diabetes model group compared with the control group.The low density lipoprotein significantly decreased in the metformin group compared with the diabetes model group. The thickness of INL siganificantly increased in the diabetes model. The thickness of INL increased in the metformin group compared with diabetes model.The thickness of IPL increased in diabetes model. The thickness of IPL dercreased in metformin group compared with diabetes model.All of cholesterol, triglyceride, SOD activity and MDA level were improved by the treatment of metformin. The tissue sections of liver and kidney induced high glucose exposure showed significant difference compared with control group, and the structures were improved by metformin treatment.Conclusion: We successfully established a diabetes model by immersing method. The levels of blood glucose, triglyceride and cholesterol significantly increased in diabetes model group compared with the control group immersed in fresh water. MDA level of the livers in the diabetes model group significantly increased, and SOD activitydecresed. The tissue sections of liver and kidney induced by high glucose exposure showed significant difference compared with control group. Metformin had therapeutic effects of the changes induced by high glucose. But metforment treatment had no improvement on the thickness of inner nuclear layer(INL) of retina.