Research Institute of Environmental Medicine Nagoya University

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Yoshitaka Hayashi
Mika Hori

Research Projects

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.

Selected Publications

  1. Hayashi Y. Glutaminostatin: Another facet of glucagon as a regulator of plasma amino acid concentrations.(Editorial) Journal of Diabetes Investigation 10:1391-1393, 2019.
  2. Liu Y, Harashima SI, Wang Y, Suzuki K, Tokumoto S, Usui R, Tatsuoka H, Tanaka D, Yabe D, Harada N, Hayashi Y, Inagaki N. Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion. FASEB J. 33(5):6239-6253.2019.
  3. Masuda A, Seino Y, Murase M, Hidaka S, Shibata M, Takayanagi T, Sugimura Y, Hayashi Y, Suzuki A.Short-Term High-Starch, Low-Protein Diet Induces Reversible Increase in β-cell Mass Independent of Body Weight Gain in Mice. Nutrients 10;11(5).2019.
  4. 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.
  5. Hori M, Ohta N, Takahashi A, Masuda H, Isoda R, Yamamoto S, Son C, Ogura M, Hosoda K, Miyamoto Y, Harada-Shiba M. Impact of LDLR and PCSK9 pathogenic variants in Japanese heterozygous familial hypercholesterolemia patients. Atherosclerosis 289:101-108,2019.
  6. Takafuji Y, Hori M, Mizuno T, Harada-Shiba M. Humoral factors secreted from adipose tissue-derived mesenchymal stem cells ameliorate atherosclerosis in Ldlr−/− mice. Cardiovascular Research 115:1041-1051,2019.
  7. Hayashi Y, Seino Y. Regulation of amino acid metabolism and alpha-cell proliferation by glucagon. Journal of Diabetes Investigation 9:464-472, 2018.
  8. Maekawa R, Seino Y, Ogata T, Murase M, Iida A, Hosokawa K, Joo E, Harada N, Tsunekawa S, Hamada Y, Oiso Y, Inagaki N, Hayashi Y, Arima H. Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice. The Journal of Nutritional Biochemistry 49: 71-79, 2017.
  9. 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.
  10. 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.
  11. 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.
  12. Fukami A, Seino Y, Ozaki N, Yamamoto M, Sugiyama C, Sakamoto-Miura E, Himeno T, Takagishi Y, Tsunekawa S, Ali S, Drucker DJ, Murata Y, Seino Y, Oiso Y, Hayashi Y. Ectopic expression of GIP in pancreatic ß-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides. Diabetes 62: 510-518, 2013.
  13. 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.
  14. Hayashi Y, Yamamoto M, Mizoguchi H, Watanabe C, Ito R, Yamamoto S, Sun XY, Murata Y. Mice deficient for glucagon gene-derived peptides display normoglycemia and hyperplasia of islet alpha-cells but not of intestinal L-cells. Molecular Endocrinology 23: 1990-1999, 2009.

(July 29, 2020)