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

Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
PLoS ONE (Impact Factor: 3.53). 04/2013; 8(1):e53913. DOI: 10.1371/journal.pone.0053913
Source: PubMed

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.

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    ABSTRACT: Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 incombination with 5-fluorouracil (5-FU) in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan-Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF) and Caspase 3) were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger antioxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.
    01/2015; 3:e859. DOI:10.7717/peerj.859
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    ABSTRACT: We previously demonstrated that cinnamon extract (CE) ameliorates type 1 diabetes induced by streptozotocin in rats through the up-regulation of glucose transporter 4 (GLUT4) translocation in both muscle and adipose tissues. This present study was aimed at clarifying the detailed mechanism(s) with which CE increases the glucose uptake in vivo and in cell culture systems using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Specific inhibitors of key enzymes in insulin signaling and AMP-activated protein kinase (AMPK) signaling pathways, as well as small interference RNA, were used to examine the role of these kinases in the CE-induced glucose uptake. The results showed that CE stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase. An AMPK inhibitor and LKB1 siRNA blocked the CE-induced glucose uptake. We also found for the first time that insulin suppressed AMPK activation in the adipocyte. To investigate the effect of CE on type 2 diabetes in vivo, we further performed oral glucose tolerance tests and insulin tolerance tests in type 2 diabetes model rats administered with CE. The CE improved glucose tolerance in oral glucose tolerance tests, but not insulin sensitivity in insulin tolerance test. In summary, these results indicate that CE ameliorates type 2 diabetes by inducing GLUT4 translocation via the AMPK signaling pathway. We also found insulin antagonistically regulates the activation of AMPK.
    PLoS ONE 02/2014; 9(2):e87894. DOI:10.1371/journal.pone.0087894 · 3.53 Impact Factor
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    ABSTRACT: Sinapic acid is a hydroxycinnamic acid contained in plants. In an attempt to know the hyperglycemic effect of sinapic acid, this study applied streptozotocin (STZ) to induce type 1-like diabetic rats and fed fructose-rich chow to induce type 2-like diabetic rats. Sinapic acid dose-dependently reduced the hyperglycemia of STZ-diabetic rats (9.8 ± 1.8 %, 11.6 ± 0.7 %, and 19.4 ± 3.2 % at 5 mg/kg, 10 mg/kg and 25 mg/kg,). Also, sinapic acid attenuated the postprandial plasma glucose without changing plasma insulin in rats. Repeated treatment of sinapic acid increased the gene expression of GLUT 4 in soleus muscle of STZ-diabetic rats. Moreover, sinapic acid enhanced glucose uptake into isolated soleus muscle and L6 cells (337.0 ± 29.6 %). Inhibition of phospholipase C (PLC) using U73122 (1.00 ± 0.02 μg/mg protein) or protein kinase C (PKC) using chelerythrine (0.97 ± 0.02 μg/mg protein) attenuated the sinapic acid-stimulated glucose uptake (1.63 ± 0.02 μg/mg protein) in L6 cells. Otherwise, the reduced glucose infusion rate (GIR) in fructose-rich chow-fed rats was also raised by sinapic acid. Our results suggest that sinapic acid ameliorates hyperglycemia through PLC-PKC signals to enhance the glucose utilization in diabetic rats.
    Journal of Agricultural and Food Chemistry 11/2013; 61(49). DOI:10.1021/jf403092b · 3.11 Impact Factor


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