Hydrogen Improves Glycemic Control in Type1 Diabetic Animal Model by Promoting Glucose Uptake into Skeletal Muscle

Akihiro Asakawa, Akio Inui, Haruka Amitani, Huhe Chaolu, Jiang-Bo Li, Kaichun Cheng, Kaori Kaimoto, Marie Amitani, Masako Nakano, Miharu Ushikai, Minglun Tsai, Mutsumi Terashi, Ryozo Kamimura, Yingxiao Li

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DOI: 10.1371/journal.pone.0053913 DOI is the universal ID for this study.

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Hydrogen (H(2)) acts as a therapeutic antioxidant. However, there are few reports on H(2) function in other capacities in diabetes mellitus (DM). Therefore, in this study, we investigated the role of H(2) in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2) promoted 2-[(14)C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2) significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p.) and oral (p.o.) administration. However, long-term p.o. administration of H(2) had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2) exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

Publish Year 2013
Country Japan
Rank Positive
Journal PLoS One
Primary Topic Whole Body
Secondary TopicDiabetes (Type I)
Model Mouse
Tertiary TopicGlucose Metabolism
Vehicle Water (Dissolved)
pH Neutral
Application Ingestion