Professor & chairman: Ryuzo KAWAMORI
Associate Professor: Yasushi TANAKA
Assistant Professor: Hirotaka Watada, Masahiko Kawasumi, Junichiro Kinoshita
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Diabetes is a serious, costly disease that is on the rise. Seven million Japanese are estimated to have Diabetes. Diabetes can cause many diseases that directly cause death, such as heart disease, stroke, blindness, kidney failure, leg and foot amputations. People with diabetes have a decreased ability to secrete insulin and/ or a decreased ability to use insulin, a hormone that allows glucose to enter cells and be converted to energy. If diabetes were not controlled well, excess glucose remain in the blood and damage a lot of organs through vessels in the whole body.
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The long term goal of the research of our department is to find the better care for diabetes subjects. To achieve this, we focus on three major subjects;
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| 1) Investigation of the role of liver in Diabetes |
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Glucose cannot be handled well in the patients with diabetes. One of the main organs that control blood glucose is liver. Soon after carbohydrates are entered into circulation, pancreatic Ącells recognize the rise of blood glucose levels and begin to secret insulin very rapidly, this rapid increase of insulin is the important determinant for glucose uptake from liver. Diabetes patients often have a defect of this rapid insulin rise and a decreased ability to use insulin(often defined as insulin resistance) of liver. Now we investigate how liver handle the glucose and why the patients cannot handle the glucose well.
As a basic research approach, we apply glucose clamp technique and common molecular biological method for rodent model of diabetes to find the important molecules for glucose handling by liver. As a clinical research approach, we establised eu-glycemic hyper-insulinemic clamp with oral glucose loading method that enabled the evaluation of glucose uptake without using any tracer in patients. Applying this method for the patients, we evaluate the importance of liver on developing diabetes.
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| 2) Investigation of factors associated with micro- and macroangiopathies in diabetes. |
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High blood glucose level is well known determinant for the progression of macro and micro angiopathy. However, the progression is not associated only with the blood glucose level.
As a clinical approach for the evaluation of the atherosclerosis, we use the intimal plus medial thickness (IMT)of the carotid artery by ultrasound high-resolution B-mode imaging. Using IMT as an index of atherosclerosis, We seek for the factor related to the atherosclerosis in diabetes patients. Especially our focus is on the genetic factors. Now we analyze a lot of SNPs encode the molecules related to atherosclerosis. These genetic diagnosis will enables us to find out the patients possessing the high risk factors for atherosclerosis and provide a suitable approach for preventing the athrosclorosis.
As a basic approach, we establish a new method for observing the initial change of atherosclerosis in rodents. Using this method, we investigate to seek the typical features of atherosclorosis caused by diabetes.
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| 3) Engineering bio-artificial pancreatic Ącell |
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A true cure for people with Diabetes can only be obtained by replacing the absent or defective Ącells. But where will we obtain these replacement cells. We think that the same pathways by which Ącells form during normal development could be used to engineer new Ącells either recapitulating islet development in culture or by inducing new islet cell formation in vivo. To do this, we need to understand how Ącells normally develop. Thus our long term objective is to understand the molecular mechanisms underlying the formation of the cells that make insulin and to apply this knowledge to the replacement of the absent or defective Ącells in patients with diabetes.
Our special interest is focused on the transcription factors implicated in the development of pancreas. Now we analyze its function and regulation of the expression for fully understand the mechanism of pancreatic development.
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