Deuterium-depleted water stimulates GLUT4 translocation in the presence of insulin, which leads to decreased blood glucose concentration

Mol Cell Biochem. 2021 Dec;476(12):4507-4516. doi: 10.1007/s11010-021-04231-0. Epub 2021 Sep 12.

Abstract

Deuterium (D) is a stable isotope of hydrogen (H) with a mass number of 2. It is present in natural waters in the form of HDO, at a concentration of 16.8 mmol/L, equivalent to 150 ppm. In a phase II clinical study, deuterium depletion reduced fasting glucose concentration and insulin resistance. In this study, we tested the effect of subnormal D-concentration on glucose metabolism in a streptozotocin (STZ)-induced diabetic rat model. Animals were randomly distributed into nine groups to test the effect of D2O (in a range of 25-150 ppm) on glucose metabolism in diabetic animals with or without insulin treatment. Serum glucose, fructose amine-, HbA1c, insulin and urine glucose levels were monitored, respectively. After the 8-week treatment, membrane-associated GLUT4 fractions from the soleus muscle were estimated by Western blot technique. Our results indicate that, in the presence of insulin, deuterium depletion markedly reduced serum levels of glucose, -fructose amine, and -HbA1c, in a dose-dependent manner. The optimal concentration of deuterium was between 125 and 140 ppm. After a 4-week period of deuterium depletion, the highest membrane-associated GLUT4 content was detected at 125 ppm. These data suggest that deuterium depletion dose-dependently enhances the effect of insulin on GLUT4 translocation and potentiates glucose uptake in diabetic rats, which explains the lower serum glucose, -fructose amine, and -HbA1c concentrations. Based on our experimental data, deuterium-depleted water could be used to treat patients with metabolic syndrome (MS) by increasing insulin sensitivity. These experiments indicate that naturally occurring deuterium has an impact on metabolic regulations.

Keywords: Deuterium (D); Deuterium depletion; Deuterium-depleted water (DDW); Diabetes mellitus (DM); GLUT-4 translocation.

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Deuterium / analysis
  • Deuterium / chemistry
  • Deuterium / metabolism*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Disease Models, Animal
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism*
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology*
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Rats
  • Rats, Wistar
  • Water / pharmacology*

Substances

  • Blood Glucose
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Slc2a4 protein, rat
  • Water
  • Deuterium