Research Institute of Environmental Medicine Nagoya University

Department of Endocrinology aims to find new strategies to prevent or control endocrinological/metabolic disorders including diabetes mellitus and hyperlipidemia. To achieve this purpose, our major approach is development and analysis of gene-modified animal models that is useful to understand pathophysiology of such disorders. Glucagon is mostly described as a hormone that increases blood glucose levels and aggravates diabetes mellitus. However, our research using a mouse model lacking glucagon gene clarified that glucagon is essential for homeostasis of amino acid metabolism.
  We also aim to elucidate the pathophysiology of hyperlipidemia and atherosclerosis to develop new preventive and therapeutic methods using genetically modified mice models, patient-derived iPS cells,and human samples.

1. Hori M, Hasegawa Y, Hayashi Y, Nakagami T, Harada-Shiba M: Acute cholesterol-lowering effect of Exendin-4 in Ldlr -/- and C57BL/6J Mice. J Atheroscler Thromb. 30:74-86, 2023.
2. Kobayashi M, Maruyama N, Yamamoto Y, Togawa T, Ida T, Yoshida M, Miyazato M, Kitada M, Hayashi Y, Kashiwagi A, Kitamura T. A newly developed glucagon sandwich ELISA is useful for more accurate glucagon evaluation than the currently used sandwich ELISA in subjects with elevated plasma proglucagon-derived peptide levels.J Diabetes Investig. 2023.　online ahead of print
3. Ueno S, Seino Y, Hidaka S, Maekawa R, Takano Y, Yamamoto M, Hori M, Yokota K, Masuda A, Himeno T, Tsunekawa S, Kamiya H, Nakamura J, Kuwata H, Fujisawa H, Shibata M, Takayanagi T, Sugimura Y, Yabe D, Hayashi Y, Suzuki A: Glucagon is essential for the homeostasis of amino acid metabolism in　response to increased protein intake. Nutrients 14: 975, 2022.
4. Hatoko T, Harada N, Tokumoto S, Yamane S, Ikeguchi-Ogura E, Kato T, Yasuda T, Tatsuoka H, Shimazu-Kuwahara S, Yabe D, Hayashi Y, Inagaki N. An analysis of intestinal morphology and incretin-producing cells using tissue optical clearing and 3-D imaging. Sci Rep. 2022 20;12(1):17530.
5. Takeda K, Nemoto KI, Hayashi Y, Yamamoto M, Sakuta R, Kimura T, Noto H Two mutations in thyroid hormone receptor beta gene (P453A and C36Y) in a family with resistance to thyroid hormone with comorbid myotonic dystrophy. Thyroid 10:11,2019.
6. Iida A, Seino Y, Fukami A, Maekawa R, Yabe D, Shimizu S, Kinoshita K, Takagi Y, Izumoto T, Ogata H, Ishikawa K, Ozaki N, Tsunekawa S, Hamada Y, Oiso Y, Arima H, Hayashi Y. Endogenous GIP ameliorates impairment of insulin secretion in proglucagon-deficient mice under moderate beta cell damage induced by streptozotocin. Diabetologia 59: 1533-1541, 2016.
7. Takano Y, Kasai K, Takagishi Y, Kikumori T, Imai T, Murata Y, Hayashi Y. Pancreatic neuroendocrine tumors in mice deficient in proglucagon-derived peptides. PLoS One 10: e0133812, 2015.
8. Kinoshita K, Ozaki N, Takagi Y, Murata Y, Oshida Y, Hayashi Y. Glucagon is essential for adaptive thermogenesis in brown adipose tissue. Endocrinology 155: 3484-3492, 2014.
9. Watanabe C, Seino Y, Miyahira H, Yamamoto M, Fukami A, Ozaki N, Takagishi Y, Sato J, Fukuwatari T, Shibata K, Oiso Y, Murata Y, Hayashi Y. Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides. Diabetes 61: 74-84, 2012

(April 9, 2023)