Matsumoto's Lab. Faculty of Life Sciences, Kyoto Sangyo University

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Obesity is considered as major cause of onset of type 2 diabetes. This idea comes from statistic data of diabetes patients past two decades. It showed a tight correlation between obesity and onset of diabetes. Of course, obesity causes many diseases in the three to five fold higher rate of diseases than non-obese. However, the rate of onset of diabetes is incredibly higher than any other diseases, as shown in the Figure. Oh, yes, it shows 10 to 50 fold higher rate than the other diseases under obesity situation. This means obesity induces type 2 diabetes specfically.

　This statistical data came from that of Western people, so that the result may not be fit to that of Japanese people. Several reports suggested that Japanese was much more susceptible to obesity than Western people. That is, Japanese are more likely to develop type 2 diabetes with less obesity than that of Western people. I suspect that our metabolic system could not adapt yet to the Western food such as meat in such short interval within 100 years, so that it seems that Western food tend to accumulate abnormally into abdominal. Many scientists warn us that visceral fat is high risk factor of onset of type 2 diabetes. In fact, insulin secretion ability in beta-cells decreases in Japanese with mild obesity.

It is well known that type 2 diabetes is familial disease. Namely, genetic factor is major cause of the disease. However, as you know well, patients of type 2 diabetes have soared skyward in the past decade. This means that environmental factor, especially obesity must be major cause of type 2 diabetes. What is the reason why type 2 diabetes increases by the increase of obesity? We suggest that patients of type 2 diabetes have some diabetogenic genes which are highly susceptible to obesity.

Prevention of obesity can decrease the incidence rate of type 2 diabetes. But obesity population is, will be growing in the world, so it looks hard to prevent the obesity, since we are always under sedentary condition by car, computer work, etc. Moreover, we are taking excess foods even under sedentary condition. It seems hard to escape such situation in developed countries. This is the reason why we have been searching diabetogenic genes responsible for obesity. If we could identify the gene responsible for type 2 diabetes with mild obesity, we can step forward to developing new medicines.

Fortunately or unfortunately, we human have vast heterogeneities in genetically, or environmentally. Even if someone share same diabetogenic genes, one guy shows diabetes but the other never because of environmental differences among them. The reverse way also exists. That is, it is hard to identify causative genes responsible for type 2 diabetes in human in genetical way. It would be nice if we had animal models of human type 2 diabetes with mild obesity, because we can make them a constant environment.

We will describe about best animal model of human type 2 diabetes with mild obesity. we call it OLETF rat. OLETF rat shows type 2 diabetes with obesity and recovers from the disease by reducing fat accumulation in the abdominal.