Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes

Abstract

Background: Saturated fatty acids (SFAs) generally have been thought to worsen insulin-resistance and increase the risk of developing type 2 diabetes mellitus (T2DM). Recently, accumulating evidence has revealed that SFAs are not a single homogeneous group, instead different SFAs are associated with T2DM in opposing directions. Pentadecanoic acid (C15:0, PA) is directly correlated with dairy products, and a negative association between circulating PA and metabolic disease risk was observed in epidemiological studies. Therefore, the role of PA in human health needs to be reinforced. Whether PA has a direct benefit on glucose metabolism and insulin sensitivity needs further investigation. Objective: The present study aimed to investigate the effect and potential mechanism of action of PA on basal and insulin stimulated glucose uptake in C2C12 myotubes. Methods: Glucose uptake was determined using a 2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino)-2deoxyglucose (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. The phosphorylation levels of proteins involved in the insulin and 5'-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined by western blotting. Results: We found that PA significantly promoted glucose uptake and GLUT4 translocation to the plasma membrane. PA had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (Tyr632) and protein kinase B (PKB/Akt), but increased phosphorylation of AMPK and Akt substrate of 160 kDa (AS160). Compound C (an AMPK inhibitor) blocked PA-induced AMPK activation and reversed PA-induced GLUT4 translocation, indicating that PA promotes glucose uptake via the AMPK pathway in vitro. Moreover, PA significantly promoted insulin-stimulated glucose uptake in myotubes. Under insulin stimulation, PA did not affect the insulin-dependent pathway, but still activated AMPK. Conclusion: PA, an odd-chain SFA, significantly stimulates glucose uptake via the AMPK-AS160 pathway and exhibits an insulin-sensitizing effect in myotubes.

Glucose metabolism enhancement by 10-hydroxy-2-decenoic acidviathe PI3K/AKT signaling pathway in high-fat-diet/streptozotocin induced type 2 diabetic mice

“…72 Further, PA significantly stimulates basal glucose uptake and promotes insulin-induced glucose uptake in C2C12 myotubes. 73 In the current study, PA levels were reversed after 10-HDA administration. Thus, based on the above metabolomics results, we speculate that 10-HDA can regulate FAHFA (16:0/18:1) and PA metabolism to interfere with T2DM development.…”

Effect of High-Fat and Low-Fat Dairy Products on Cardiometabolic Risk Factors and Immune Function in a Low Birthweight Swine Model of Diet-Induced Insulin Resistance

“…Meta-analyses of cohort studies have previously reported an inverse relationship between biomarkers of dairy fat intake, particularly the C15:0 and C17:0, and the incident of T2D in humans (14,40). In vitro studies have also reported that C15:0 play a direct role in glucose metabolism via promoting GLUT4 translocation to plasma membrane in myotubes (41). C15:0 has also recently been proposed to be an essential fatty acid due to a number of established cardiometabolic benefits including attenuation of glucose concentrations in mice fed with high-fat diet (13).…”

Hydroxysafflor Yellow A Alters Fuel Selection From Glucose to Fat by Activating the PPARδ Pathway in Myocytes

“…According to Fu's procedure, 2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino)-2-deoxyglucose (2-NBDG, Amgicam) was used to determine cellular glucose uptake. 29 C2C12 cells were differentiated in 96-well plates for 3 d and treated with different concentrations of HSYA for 24 h, or C2C12 cells were differentiated in 6-well plates for 3 d and transfected with siPPARδ as previously described, followed by treatment with 0.122 mg/mL of HSYA for 24 h. Then, the medium was replaced with serum-free DMEM containing 5 mM glucose. After 4 h incubation, the cells were incubated with the same medium containing 80 μM 2-NBDG with or without 100 nm insulin for 30 min at 37 °C.…”