title: Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes.
abstract: OBJECTIVE
  In previous studies, hydrogen gas (H2)administration has clearly shown effectiveness in inhibiting diabetes. Here, we evaluated whether subcutaneous injection of H2shows enhanced efficacy against type 2 diabetes mellitus induced in mice by a high-fat diet and low-dose streptozotocin treatment.
  
  
  METHODS
  H2was injected subcutaneously at a dose of 1 mL/mouse/week for 4 weeks. Type 2 diabetes mellitus-associated parameters were then evaluated to determine the effectiveness of subcutaneous H2administration.
  
  
  RESULTS
  The bodyweight of H2-treated mice did not change over the course of the experiment. Compared with the untreated control animals, glucose, insulin, low-density lipoprotein and triglyceride levels in the serum were significantly lower in treated mice, whereas high-density lipoprotein cholesterol in the serum was significantly higher. Glucose tolerance and insulin sensitivity were both improved in H2-treated mice. Diabetic nephropathy analysis showed significant reductions in urine volume, urinary total protein and β2-microglobulin, kidney/bodyweight ratio, and kidney fibrosis associated with subcutaneous injection of H2.
  
  
  CONCLUSIONS
  Subcutaneous injection of H2significantly improves type 2 diabetes mellitus and diabetic nephropathy-related outcomes in a mouse model, supporting further consideration of subcutaneous injection as a novel and effective route of clinical H2administration.
authors.affiliation: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Preventive Medicine, School of Environmental Science and Management, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Keke
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Xu
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, Ningbo, Zhejiang Province, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Mimi
authors.initials: M
authors.lastname: Kong
authors.affiliation: Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Fangyan
authors.identifier: http://orcid.org/0000-0003-0555-8495
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000628:therapy; D059305:Diet, High-Fat; D006859:Hydrogen / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D013311:Streptozocin
chemical_list: D013311:Streptozocin; D006859:Hydrogen
keywords: Diabetic nephropathy; Hydrogen; Subcutaneous administration