title: Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.
abstract: 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.
authors: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Haruka
authors: H
authors: Amitani
authors: Akihiro
authors: A
authors: Asakawa
authors: Kaichun
authors: K
authors: Cheng
authors: Marie
authors: M
authors: Amitani
authors: Kaori
authors: K
authors: Kaimoto
authors: Masako
authors: M
authors: Nakano
authors: Miharu
authors: M
authors: Ushikai
authors: Yingxiao
authors: Y
authors: Li
authors: Minglun
authors: M
authors: Tsai
authors: Jiang-Bo
authors: JB
authors: Li
authors: Mutsumi
authors: M
authors: Terashi
authors: Huhe
authors: H
authors: Chaolu
authors: Ryozo
authors: R
authors: Kamimura
authors: Akio
authors: A
authors: Inui
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006859:Hydrogen / Q000008:administration & dosage*; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D001786:Blood Glucose; D005947:Glucose; D051275:Glucose Transporter Type 4; D006859:Hydrogen; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D011494:Protein Kinases; C495693:Slc2a4 protein, mouse