<i>Cyclocarya paliurus</i> extract activates insulin signaling via Sirtuin1 in C2C12 myotubes and decreases blood glucose level in mice with impaired insulin secretion

<div><p>Diabetes is caused by the lack of release or action of insulin. Some foods and supplements can compensate for this deficiency; thus, they can aid in the prevention or treatment of diabetes. The aim of this study was to investigate the effects of Cyclocarya paliurus extract (CPE) on insulin signaling and its capacity to correct hyperglycemia in the absence of insulin. To investigate the hypoglycemic effects of CPE, C2C12 cells were exposed to CPE (50 and 100 μg/mL). CPE promoted 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2NBDG) uptake into the cells via translocation of glucose transporter 4 (Glut4) to the plasma membrane. In addition, CPE enhanced tyrosine phosphorylation of insulin receptor substrate and activated phosphatidylinositol 3-kinase and protein kinase B (Akt) via sirtuin1 in C2C12 cells. Moreover, we found that oral administration of CPE (1 g/kg) to streptozotocin-induced hyperglycemic mice produced a progressive decrease in plasma glucose levels at 1 h after single dosing. At that point, CPE significantly increased the expression of skeletal muscle membrane Glut4 and enhanced the phosphorylation of Akt. These results suggest that CPE exerts antidiabetic effects similar to those of insulin, and may be an oral therapeutic alternative for the management of diabetes.</p></div

Typical EDXS of xerogels originate from CTAB-GO gels in cyclopentanone.

<p>The Cu and Au peaks originate from the substrate of copper foil and the coated gold nanoparticles.</p

TG curves of xerogels.

<p>(A) GO sheet and C16Py-GO gels in DMF, THF, and pyridine; (B) GO sheet and BPy-GO gels in DMF, cyclopentanone, and THF; (C) GO sheet and CTAB-GO gels in DMF, cyclopentanone, cyclohexanone, 1,4-dioxane, and THF.</p

Oral administration of CPE decreased blood glucose level in STZ-induced diabetic mice.

<p>ICR mice were injected intraperitoneally with a single dose of STZ (200 mg/kg) and randomly divided into 2 groups, a control group (Cont) and a CPE administration group (CPE). Mice injected with an equal volume of saline were maintained as normal groups (Nor). Blood glucose levels at 1 and 2 h after oral administration of CPE (1 g/kg) to STZ-induced diabetic mice (A), and the change from before administration (B). Blood insulin concentrations (C) and phosphorylation level of AS160 and Akt in the skeletal muscles (D) at 1 h after administration. Data are expressed as the mean ± SEM (<i>n</i> = 5–9) *<i>p</i> < 0.05, **<i>p</i> < 0.01 <i>vs</i>. the control group.</p

XRD patterns of xerogels.

<p>(A) GO sheets; (B) C16Py-GO gels in DMF (a), THF (b), and pyridine (c); (C) BPy-GO gels in DMF (a), cyclopentanone (b), and THF (c); (D) CTAB-GO gels in DMF (a), cyclopentanone (b), cyclohexanone (c), 1,4-dioxane (d), and THF (e).</p

SEM images of xerogels. GO sheets (a), C16Py-GO gels ((b) DMF, (c) THF, and (d) pyridine), BPy-GO gels ((e) DMF, (f) cyclopentanone, and (g) THF), and CTAB-GO gels ((h) DMF, (i) cyclopentanone, (j) cyclohexanone, (k) 1,4-dioxane, and (l) THF).

<p>SEM images of xerogels. GO sheets (a), C16Py-GO gels ((b) DMF, (c) THF, and (d) pyridine), BPy-GO gels ((e) DMF, (f) cyclopentanone, and (g) THF), and CTAB-GO gels ((h) DMF, (i) cyclopentanone, (j) cyclohexanone, (k) 1,4-dioxane, and (l) THF).</p

TGA data of GO sheet and amphiphiles-GO xerogels.

<p>TGA data of GO sheet and amphiphiles-GO xerogels.</p

CPE activated PI3K-Akt-AS160 signaling in C2C12 cells.

<p>C2C12 cells were exposed to CPE (50 or 100 μg/mL) or insulin (100 nM) for 30 min. The phosphorylation level of AS160 at Thr642 (A), Akt at Ser473 and Thr308 (B), and effects of CPE on the 2NBDG uptake in C2C12 cells treated with 50 μM Perifosine, Akt inhibitor (C). IRS1 and p85 subunit of PI3K complex (D) was determined by immunoprecipitation. Data are expressed as the mean ± SEM of three independent experiments. **<i>p</i> < 0.01 <i>vs</i>. the vehicle-treated control.</p

CPE affected IRS1 but not insulin receptor in C2C12 cells.

<p>Tyrosine phosphorylation level of IRS1 (A), phosphorylation level of IRS1 at serine307, 318, 612 and 1101 (B) were investigated. Effects of CPE on the 2NBDG uptake (C) and phosphorylation level of Akt (D) in C2C12 cells treated with 100 μM HNMPA(AM)₃, p-IR inhibitor. Data are expressed as the mean ± SEM of three independent experiments. **<i>p</i> < 0.01 <i>vs</i>. the vehicle-treated control.</p

Additional file 1: of Graphene Oxide-Polymer Composite Langmuir Films Constructed by Interfacial Thiol-Ene Photopolymerization

Supporting information. (DOCX 5395 kb