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Modulatory effects of miracle fruit ethanolic extracts on glucose uptake through the insulin signaling pathway in C2C12 mouse myotubes cells.

ABSTRACT: Miracle fruit, Synsepalum dulcificum, is commonly known to be an alternative sweetener. It makes sour food taste sweet by affecting the tongue's taste receptors. It also shows beneficial health effects, such as antioxidant, anti-inflammatory, and antihyperglycemic activities. This study was conducted to investigate the antidiabetic effects of miracle fruit flesh (MF) and seed (MS) ethanolic extracts and the underlying mechanisms. Differentiated C2C12 myotubes were treated with the MF or MS extract (1-1,000 ?g/ml) or metformin (1 mM) in the presence or absence of insulin. Compared with metformin, the MF extract significantly increased the intake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG). The MF extract also upregulated insulin receptor, phosphatidylinositol 3-kinase, and glucose transporter 4 expressions. These results reveal the antidiabetic effects of miracle fruit.

SUBMITTER: Han YC

PROVIDER: S-EPMC6418466 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Modulatory effects of miracle fruit ethanolic extracts on glucose uptake through the insulin signaling pathway in C2C12 mouse myotubes cells.

Han Yi-Chun YC Wu Ju-Yu JY Wang Chin-Kun CK

Food science & nutrition 20190205 3

Miracle fruit, <i>Synsepalum dulcificum</i>, is commonly known to be an alternative sweetener. It makes sour food taste sweet by affecting the tongue's taste receptors. It also shows beneficial health effects, such as antioxidant, anti-inflammatory, and antihyperglycemic activities. This study was conducted to investigate the antidiabetic effects of miracle fruit flesh (MF) and seed (MS) ethanolic extracts and the underlying mechanisms. Differentiated C2C12 myotubes were treated with the MF or M ...[more]

PMID: 30918646

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Project description:BACKGROUND:Alisol A-24-acetate (AA-24-a) is one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., which possesses multiple biological activities, including a hypoglycemic effect. Whether AA-24-a is a hypoglycemic-active compound of A. orientale (Sam.) Juz. is unclear. The present study aimed to clarify the effect and potential mechanism of action of AA-24-a on glucose uptake in C2C12 myotubes. METHOD:Effects of AA-24-a on glucose uptake and GLUT4 translocation to the plasma membrane were evaluated. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. To determine the underlying mechanism, the phosphorylation levels of proteins involved in the insulin and 5'-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined using western blotting. Furthermore, specific inhibitors of key enzymes in AMPK signaling pathway were used to examine the role of these kinases in the AA-24-a-induced glucose uptake and GLUT4 translocation. RESULTS:We found that AA-24-a significantly promoted glucose uptake and GLUT4 translocation in C2C12 myotubes. AA-24-a increased the phosphorylation of AMPK, but had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/AKT). In addition, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the AKT substrate of 160 kDa (AS160), two proteins that act downstream of AMPK, was upregulated. Compound C, an AMPK inhibitor, blocked AA-24-a-induced AMPK pathway activation and reversed AA-24-a-induced glucose uptake and GLUT4 translocation to the plasma membrane, indicating that AA-24-a promotes glucose metabolism via the AMPK pathway in vitro. STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, also attenuated AA-24-a-induced glucose uptake and GLUT4 translocation. Moreover, STO-609 weakened AA-24-a-induced phosphorylation of AMPK, p38 MAPK and AS160. CONCLUSIONS:These results indicate that AA-24-a isolated from A. orientale (Sam.) Juz. significantly enhances glucose uptake via the CaMKKβ-AMPK-p38 MAPK/AS160 pathway.

Dataset Information

Modulatory effects of miracle fruit ethanolic extracts on glucose uptake through the insulin signaling pathway in C2C12 mouse myotubes cells.

Publications

Modulatory effects of miracle fruit ethanolic extracts on glucose uptake through the insulin signaling pathway in C2C12 mouse myotubes cells.

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