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Rhonda D Prisby Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Joshua M Swift Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Susan A Bloomfield Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Harry A Hogan Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Michael D Delp Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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declines in bone structural and mechanical properties are observed in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes and 2) to determine whether possible declines in BMD and bone mechanical properties coincide with the onset and progression

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Tetsuhiro Kakimoto Safety Research Laboratory, Department I, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan

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Hirotaka Kimata Safety Research Laboratory, Department I, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan

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Satoshi Iwasaki Safety Research Laboratory, Department I, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan

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Atsushi Fukunari Safety Research Laboratory, Department I, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan

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Hiroyuki Utsumi Safety Research Laboratory, Department I, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan

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and pancreatic islet histology in Zucker diabetic fatty (ZDF) rats, which has not been sufficiently investigated ( Finegood et al . 2001 ). The ZDF rat strain is of increasing preclinical interest, because of its pathophysiological similarities to

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Raylene A Reimer Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4
Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4

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Gary J Grover Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4
Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4

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Lee Koetzner Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4

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Roland J Gahler Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4

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Michael R Lyon Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4
Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4

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Simon Wood Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4
Faculty of Kinesiology, Department of Biochemistry and Molecular Biology, Product Safety Labs, Department of Physiology and Biophysics, Factors Group of Nutritional Companies, Canadian Centre for Functional Medicine, University of British Columbia, Faculty of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4

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for Care and Use of Laboratory Animals. Sixty six male Zucker diabetic fatty rats (ZDF)/Crl- Leprfa/fa rats were obtained from Charles River (Kingston, NY, USA) at 7–8 week of age and individually housed in a temperature (19–22 °C) and humidity

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Tetsuhiro Kakimoto Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Kinya Okada Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Yoshihiro Hirohashi Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Raissa Relator Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Mizue Kawai Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Taku Iguchi Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Keisuke Fujitaka Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Masashi Nishio Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Tsuyoshi Kato Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Atsushi Fukunari Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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Hiroyuki Utsumi Safety Research Laboratories, Advanced Medical Research Laboratories, Faculty of Science and Engineering, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan

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diabetic nephropathy, such as Zucker diabetic fatty rats and Otsuka Long-Evans Tokushima fatty (OLETF) rats ( Floege et al . 1992 , Hoshi et al . 2002 , Herrmann et al . 2012 , Sofue et al . 2012 ). Accordingly, the quantification of glomerular

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Rengasamy Palanivel Department of Biology, York University, Toronto, Ontario, Canada M3J 1P3

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Vivian Vu Department of Biology, York University, Toronto, Ontario, Canada M3J 1P3

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Min Park Department of Biology, York University, Toronto, Ontario, Canada M3J 1P3

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Xiangping Fang Department of Biology, York University, Toronto, Ontario, Canada M3J 1P3

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Gary Sweeney Department of Biology, York University, Toronto, Ontario, Canada M3J 1P3

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increased by 34% and there was no significant difference in free fatty acid levels (0.0245±0.0049 vs 0.0220±0.0072 mM respectively). Figure 5 Changes in the adipokine profile level in wild-type versus STZ-diabetic rat adipocyte-conditioned medium. The level

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Victor Wong Department of Medicine, Division of Endocrinology and Metabolism and the Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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Linda Szeto Department of Medicine, Division of Endocrinology and Metabolism and the Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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Kristine Uffelman Department of Medicine, Division of Endocrinology and Metabolism and the Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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I George Fantus Department of Medicine, Division of Endocrinology and Metabolism and the Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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Gary F Lewis Department of Medicine, Division of Endocrinology and Metabolism and the Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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phosphorylation in Zucker fatty rat skeletal muscle We next examined insulin-signaling proteins downstream of IRS-1 and the results are illustrated in Fig. 2 . Akt protein levels did not differ among the groups in this study. Insulin-stimulated Akt

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Martina Holubová Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

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Jana Zemenová Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Department of Analytical Chemistry, University of Chemistry and Technology, Prague, Czech Republic

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Barbora Mikulášková Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

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Vladimíra Panajotova Apigenex Limited, Prague, Czech Republic

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Jiří Stöhr Apigenex Limited, Prague, Czech Republic

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Martin Haluzík First Faculty of Medicine, Charles University, Prague, Czech Republic

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Jaroslav Kuneš Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

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Blanka Železná Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

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Lenka Maletínská Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

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standard diet. In addition to the DIO rat model, the Zucker diabetic rat model, which is a model with impaired leptin receptor signaling ( Fellmann et al . 2013 ), is frequently used for studying the potential of anti-obesity and anti-diabetic peptidic

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Yi Lin Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center (OUHSC), BMSB 662A, PO Box 26901, 940 SL Young Boulevard, Oklahoma City, Oklahoma 73104, USA

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Zhongjie Sun Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center (OUHSC), BMSB 662A, PO Box 26901, 940 SL Young Boulevard, Oklahoma City, Oklahoma 73104, USA

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; require small sample size Homogenous and monogenic inheritance unlike heterogeneity seen in human T2DM Zucker diabetic fatty (ZDF) rat ( Shafrir 1992 ) Hyperglycemia and insulin resistance. Male ZDF rat exhibits impaired insulin secretory β-cell response

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Victor P Bilan Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of
Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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Eman M Salah Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of
Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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Sheldon Bastacky Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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Huw B Jones Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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Rachel M Mayers Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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Bradley Zinker Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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Simon M Poucher Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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Stevan P Tofovic Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of
Division of Pulmonary, Medicine, Pathology, Pathology, CVGI Discovery, Diabetes Drug Discovery, Allergy, and Critical Care Medicine, Vascular Medicine Institute, Departments of

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mutations ( fa and fa cp ): the lean female Zucker diabetic fatty rat (ZDF; +/ fa ) and the lean male spontaneously hypertensive heart failure rat (SHHF; +/ fa cp ) derived from the obese spontaneously hypertensive rat carrying the corpulent fa cp gene

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Yuichi Kikuchi Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Muneharu Yamada Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Toshihiko Imakiire Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Taketoshi Kushiyama Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Keishi Higashi Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Naomi Hyodo Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Kojiro Yamamoto Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Takashi Oda Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Shigenobu Suzuki Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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Soichiro Miura Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

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-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes 41 1422 –1428. Kikuchi Y , Imakiire T, Yamada M, Saigusa T, Hyodo T, Hyodo N, Suzuki S & Miura S 2005 Mizoribine reduces

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