Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle

PLoS One. 2013;8(1):e53913. doi: 10.1371/journal.pone.0053913. Epub 2013 Jan 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Cricetinae
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diet, High-Fat
  • Disease Models, Animal
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Hep G2 Cells
  • Humans
  • Hydrogen / administration & dosage*
  • Mice
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase C / metabolism
  • Protein Kinases / metabolism

Substances

  • Blood Glucose
  • Glucose Transporter Type 4
  • Slc2a4 protein, mouse
  • Hydrogen
  • Protein Kinases
  • AMP-activated protein kinase kinase
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase C
  • Glucose

Grant support

This research is partially funded by the Young Researcher Overseas Visits Program for Vitalizing Brain Circulation of the Japan Society for the Promotion of Science. The authors gratefully acknowledge VANA Co., Ltd. (Yamanashi, Japan) for the generous gift of natural hydrogen water. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.