Stimulation of leptin secretion by insulin

Leptin has a crucial role in regulating food intake and maintaining metabolic homeostasis. Although little is known about the process of leptin secretion, insulin, which has an important role in the metabolism of glucose and lipids, is believed to regulate leptin secretion through a posttranscriptional mechanism in the short term, and via glucose metabolism in the long term. The gastric mucosa secretes leptin, but this mechanism has not been completely elucidated. Understanding the mechanism of insulin-regulated leptin secretion could lead to the development of new treatment methods for obesity and its comorbidities, which are serious public health concerns

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

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

The effect of i.p. administration of H₂ on hyperglycemia in STZ-treated mice.

<p>(A) Blood glucose in the group injected with high-content hydrogen saline (HHS) after STZ administration was significantly lower than the control group at every 7-days-interval measurement (n = 16 for each group). (B, C) Body weight and food intake every 7 day are shown. Although there was no significant difference in body weights or food intake between the control and HHS groups (n = 16 for each group), the food intake in the HHS group showed a tendency to decrease. (D, E) Blood glucose in the HHS group in the day-30 IPGTT was significantly lower than the control group at 5, 30, 60 and 120 min, and the area under the curve (AUC) of the HHS group was significantly lower than control (n = 16 for each group). (F) Membrane Glut4 in the HHS group was significantly increased compared to the control group, as determined by western blot analysis (n = 6 for each group). (G) Although there was no significant difference in cytosolic Glut4 between groups, the cytosolic Glut4 in the HHS group showed a tendency to decrease (n = 4 for each group). The bar graph shows the ratio of each protein to actin protein bands quantified by densitometric analysis. Comparisons with controls were performed by unpaired Student’s t test between two groups. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001.</p

Laboratory investigations in the chronic p.o. administration of H₂ experiment with STZ-induced T1DM mice.

<p>Data are expressed as mean ± standard error (SE). Comparisons with control group were performed by Dunnett’s multiple comparison test. As described in Materials and Methods, we lost several mice accidentally and therefore combined two groups [LHW group (n = 2) and HHW group (n = 2)] data together. STZ = streptozotocin; T1DM = type 1 diabetes mellitus; LHW = low content hydrogen water; HHW = high content hydrogen water; NHW = natural hydrogen water; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NEFA = free fatty acids; BUN = blood urea nitrogen; AST = aspartate aminotransferase; ALT = alanine aminotransferase; γ-GTP = γ-glutamyl transpeptidase.</p>*<p>P<0.05,</p>**<p>P<0.01.</p