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Researcher Information

last modified:2019/03/05

Associate Professor MISU Hirofumi


Faculty, Affiliation

Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences
Associate Professor

College and School Educational Field


 TEL:076-265-2234 FAX:076-234-4250

Academic Background

【Academic background(Bachelor's Degree)】
Kanazawa University
MD. PhD.


Year & Month of Birth


Academic Society


○JDDW 2015 Best Presenter Award in International Session(2015/12/02)
○JDDW 2015 Best Presenter Award in International Session(2015/12/02)
○JDDW 2015 Best Presenter Award in International Session(2015/12/02)
○JDDW 2015 Best Presenter Award in International Session(2015/12/02)



Speciality Keywords

Type 2 Diabetes, Insulin Resistance, Hepatokine, selenoprotein P, reactive oxygen species, LECT2

Research Themes

Elucidation of homeostatic mechanism by liver through production of hepatokines

Elucidation of homeostatic mechanism by liver through production of hepatokines

Development of exercise enhancing drugs targeting hepatokine selenoprotein P

Development of exercise enhancing drugs targeting hepatokine selenoprotein P

Identification and functional analysis of hepatokines involved in obesity

Development of novel therapies for type 2 diabetes targeting liver-derived secretory proteins, "hepatokines"



  •  Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle Hirofumi Misu et al. Nature Medicine 23 4 508-516 2017/02/28
  •  A liver-derived secretory protein, selenoprotein P, causes insulin resistance  Hirofumi Misu, Toshinari Takamura et al. Cell Metabolism 12 5 483-495 2010/11
  •  Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models. Hirofumi Misu (co-authror) Nature Communications 8 1658 2017
  •  LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance. Diabetes 63 1649-1664 2014/01
  •  Selenoprotein P as a diabetes-associated hepatokine that impairs angiogenesis by inducing VEGF resistance in vascular endothelial cells Diabetologia 57 9 1968-1976 2014/07

show all

  •  Proteasome dysfunction mediates obesity-induced endoplasmic reticulum stress and insulin resistance in the liver. Diabetes 62 3 811-824 2013/03
  •  Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes Diabetologia 50 268-277 2007/11
  •  Metformin suppresses expression of the selenoprotein P gene via an AMP-activated kinase (AMPK)/FoxO3a pathway in H4IIEC3 hepatocytes. JOURNAL OF BIOLOGICAL CHEMISTRY 289 1 335-345 2014/01
  •  The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia E pub. 2014/01
  •  Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice Keita Chikamoto, Hirofumi Misu, et al. Biochemical and Biophysical Research Communications 478 1310-1316
  •  Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes. PLoS ONE 7 4 e34952 2012/04
  •  Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis.  Hepatology 48 1 109-118 2008/07
  •  Insulin Resistance Accelerates a Dietary Rat Model of Nonalcoholic Steatohepatitis. GASTROENTEROLOGY 132 1 282-293 2007/01
  •  Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis Liver International In press
  •  Concentration-dependent Dual Effects of Hydrogen Peroxide on Insulin Signal Transduction in H4IIEC Hepatocytes PLoS ONE 6 11 27401 2011/11
  •   Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. JOURNAL OF BIOLOGICAL CHEMISTRY 284 22 14809-14818 2009/05
  •  Factors associated with improvement of fasting plasma glucose level by mealtime dosing of a rapid-acting insulin analog in type 2 diabetes. DIABETES RESEARCH AND CLINICAL PRACTICE 75 3 278-284 2007/03
  •  Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. HEPATOLOGY 46 5 1392-1403 2007/11
  •  Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic Fatty liver disease PLoS One 9 3 e92170 2014/03
  •  Obesity Upregulates Genes Involved in Oxidative Phosphorylation in Livers of Diabetic Patients. Obesity (Silver Spring). 16 12 2601-2609 2008/12
  •  Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes. DIABETES RESEARCH AND CLINICAL PRACTICE 71 3 241-246 2006/03
  •  The hepatic circadian clock is preserved in a lipid-induced mouse model of non-alcoholic steatohepatitis. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 380 3 684-688 2009/03
  •  Gene expression profiles in peripheral blood mononuclear cells reflect the pathophysiology of type 2 diabetes. Biochem Biophys Res Commun 361 2 379-384 2007/09
  •  Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. Metabolism 57 8 1071-1077 2008/08
  •  Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis. PLoS ONE e43056 2012/09
  •  Regulation of adiponectin receptor expression in human liver and a hepatocyte cell line. Metabolism 56 11 1478-1485 2007/11
  •  Fatty liver as a consequence and cause of insulin resistance: lessons from type 2 diabetic liver. ENDOCRINE JOURNAL 59 9 745-763 2012/08
  •  Transformation of p53-positive papillary thyroid carcinoma to anaplastic carcinoma of the liver following postoperative radioactive iodine-131 therapy. INTERNAL MEDICINE 47 19 1709-1712 2008/09
  •  Duodenal adenocarcinoma with neuroendocrine features in a patient with acromegaly and thyroid papillary adenocarcinoma: a unique combination of endocrine neoplasia. ENDOCRINE JOURNAL 59 9 791-796 2012/05
  •  Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects. EUROPEAN JOURNAL OF PHARMACOLOGY 588 23 316-324 2008/07
  •  Pharmacokinetics and pharmacodynamics of insulin aspart in patients with type 2 diabetes: assessment using a meal tolerance test under clinical conditions. Clin Exp Pharmacol Physiol. 39 6 528-534 2012/06
  •  Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance: implications for type 2 diabetes. Metabolism 61 10 1388-1394 2012/04
  •  Slowly progressive insulin-dependent diabetes in a patient with primary biliary cirrhosis with portal hypertension-type progression. INTERNAL MEDICINE 51 1 79-82 2012/01
  •  Cushing's syndrome and big IGF-II associated hypoglycaemia in a patient with adrenocortical carcinoma. BMC Case Rep. E pub. 2010/03
  •  SAGE application in the study of diabetes. Curr Pharm Biotechnol. 9 5 392-399 2008/09
  •  Urinary Kim-1 is a sensitive biomarker for the early stage of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats Diab Vasc Dis Res 11 4 243-250 2014
  •  Regulation of the physiological effects of peroxidovanadium(V) complexes by the electronic nature of ligands J Inorg Biochem 121 66-76 2013
  •  Inhibin betaE (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples PLoS One 13 3 e0194798 2018
  •  Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study BMJ Open Diabetes Res Care 6 1 e000469 2018
  •  The influence of adiposity and acute exercise on circulating hepatokines in normal-weight and overweight/obese men Appl Physiol Nutr Metab 43 5 482-490 2018
  •  Eicosapentaenoic acid down-regulates expression of the selenoprotein P gene by inhibiting SREBP-1c protein independently of the AMP-activated protein kinase pathway in H4IIEC3 hepatocytes J Biol Chem 292 26 10791-10800 2017/06/30
  •  Endogenous Selenoprotein P, a Liver-Derived Secretory Protein, Mediates Myocardial Ischemia/Reperfusion Injury in Mice Int J Mol Sci 19 3 epub ahead of print 2018

Conference Presentations

Arts and Fieldwork


Theme to the desired joint research

○Development of novel diagnostic methods for diabetes targeting hepatokines
○The development of novel therapies for diabetes targeting "hepatokines"

Grant-in-Aid for Scientific Research

○「新規インスリン抵抗性ヘパトカインセレノプロテインPを標的とした糖尿病治療法の探索 」(2011-2013) 

Classes (Bachelors)

○Clinical Nutrition Support(2017)
○Clinical Nutrition Support(2017)
○Clinical Nutrition Support(2017)
○Clinical Nutrition Support(2017)
○Clinical Nutrition Support(2016)

Classes (Graduate Schools)

○Topics in Biochemical Engineering 1(2017)
○Comprehensive Metabology(2017)
○Comprehensive Metabology(2017)
○Comprehensive Metabology(2016)
○Comprehensive Metabology(2016)
○Topics in Biochemical Engineering 1(2016)

International Project

International Students

Lecture themes

Others (Social Activities)

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