scholarly journals miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir

2019 ◽  
Vol 10 ◽  
Author(s):  
Elena Bresciani ◽  
Cecilia Saletti ◽  
Nicola Squillace ◽  
Laura Rizzi ◽  
Laura Molteni ◽  
...  
Planta Medica ◽  
2019 ◽  
Vol 85 (05) ◽  
pp. 412-423 ◽  
Author(s):  
Abraham Giacoman-Martínez ◽  
Francisco Alarcón-Aguilar ◽  
Alejandro Zamilpa ◽  
Sergio Hidalgo-Figueroa ◽  
Gabriel Navarrete-Vázquez ◽  
...  

Abstract Hibiscus sabdariffa is a medicinal plant consumed as a diuretic and anti-obesity remedy. Several pharmacological studies have shown its beneficial effects in metabolism. Peroxisome proliferator-activated receptors δ and γ may play a role in the actions of H. sabdariffa. These nuclear receptors regulate lipid and glucose metabolism and are therapeutic targets for type 2 diabetes. This research aimed to perform a phytochemical study guided by a bioassay from H. sabdariffa to identify compounds with peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ agonist activity, supported by messenger ribonucleic acid expression, molecular docking, lipid accumulation, and an antihyperglycemic effect. An oral glucose tolerance test in mice with the aqueous extract of H. sabdariffa and the dichloromethane extract of H. sabdariffa was performed. The dichloromethane extract of H. sabdariffa exhibited an antihyperglycemic effect. The dichloromethane extract of H. sabdariffa was fractioned, and four fractions were evaluated in 3T3-L1 adipocytes on peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 messenger ribonucleic acid expression. Fraction F3 exhibited peroxisome proliferator-activated receptor δ/γ dual agonist activity, and a further fractionation yielded two subfractions, F3-1 and F3-2, which also increased peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ expression. Subfractions were analyzed by GC/MS. The main compounds identified in F3-1 were linoleic acid, oleic acid, and palmitic acid, while in F3-2, the main compounds identified were α-amyrin and lupeol. These molecules were subjected to molecular docking analysis. α-Amyrin and lupeol showed the highest affinity. Moreover, both produced an increase in peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 expression. Additionally, α-amyrin and lupeol decreased lipid accumulation in 3T3-L1 adipocytes and blood glucose in mice. Until now, α-amyrin and lupeol have not been reported with activity on peroxisome proliferator-activated receptors. This study provides evidence that α-amyrin and lupeol possess antidiabetic effects through a peroxisome proliferator-activated receptor δ/γ dual agonist action.


Phytomedicine ◽  
2017 ◽  
Vol 32 ◽  
pp. 74-79 ◽  
Author(s):  
Salvatore Genovese ◽  
Hitoshi Ashida ◽  
Yoko Yamashita ◽  
Tomoya Nakgano ◽  
Masaki Ikeda ◽  
...  

2021 ◽  
Vol 13 (3) ◽  
pp. 102-108
Author(s):  
Yilin Zhang ◽  
Guantai Ni ◽  
Hongying Yang

Plumbagin, a bioactive phytoconstituent, is isolated from the root of Plumbago zeylanica L. Plumbagin pos-sesses antidiabetic effect to mediate glucose homeostasis, wound healing and diabetic nephropathy. However, the involvement of plumbagin in gestational diabetes mellitus (GDM) has not been reported yet. Trophoblast cell line (HTR8/SVneo) was incubated with high glucose to establish cell model of GDM. Cell viability and proliferation were detected by MTT and EdU staining. Flow cytometry was used to investigate cell apoptosis. Cell viability of HTR8/SVneo was reduced by high glucose or incubation of plumbagin. Plumbagin restored reduced cell viability and proliferation of HTR8/SVneo induced by high glucose. Plumbagin attenuated high glucose-induced cell apoptosis in HTR8/SVneo cells through upregulation of Bcl-2 and down-regulation of Bax, cleaved caspase-3 and cleaved caspase-9. Protein expression of glucose transporter type 4 (GLUT-4), insulin receptor (INSR)-B and INSR substrate (IRS1) was decreased in high glucose-induced HTR8/SVneo but increased by plumbagin. The suppressive effects of high glucose on phosphorylation of AKT and mTOR in HTR8/SVneo were reversed by plumbagin. Plumbagin improved high glucose-induced cell apoptosis and insulin resistance of HTR8/SVneo through activation of AKT/mTOR pathway, suggesting that plumbagin might be used as a potential strategy for the prevention of GDM.


2019 ◽  
Vol 97 (9) ◽  
pp. 3907-3919 ◽  
Author(s):  
Hang Lu ◽  
Imke Kühn ◽  
Mike R Bedford ◽  
Hayley Whitfield ◽  
Charles Brearley ◽  
...  

Abstract The objective of this present study was to determine the effects of phytase dosing on growth performance, mineral digestibility, phytate breakdown, and the level of glucose transporter type 4 (GLUT4) in muscle plasma membranes of weanling pigs. A total of 160 barrows were used in a randomized completely block design and assigned to 4 treatments for a 7-wk study. Depending on the feeding phase, diets differed in dietary calcium (Ca) and phosphorus (P) levels (positive control [PC]: 8 to 6.8g/kg Ca; 7.3 to 6.3 g/kg P; negative control [NC]: 5.5 to 5.2 g/kg Ca; 5.4 to 4.7 g/kg P). NC diets were supplemented with phytase at 0 (NC); 500 (NC + 500 FTU); or 2,000 FTU/kg (NC + 2,000 FTU) phytase units/kg. Blood was collected after fasting (day 48) or feeding (day 49) for measurement of plasma inositol concentrations. On day 49, 2 pigs per pen were euthanized, and duodenal and ileal digesta samples were collected to determine inositol phosphates (InsP6-2) concentrations. High phytase supplementation increased BW on days 21, 35, and 49 (P < 0.05). Over the entire feeding period, ADG, ADFI, and feed efficiency were increased by NC + 2,000 FTU compared with the other treatments (P < 0.05). Postprandial plasma inositol concentration was increased in NC + 2,000 (P < 0.01), but there was only a tendency (P = 0.06) of a higher fasting plasma inositol concentration in this group. Inositol concentrations in the portal vein plasma (day 49) were not different among treatments. Duodenal digesta InsP5 and InsP6 concentrations were similar in PC and NC, but higher in these 2 treatments (P < 0.05) than those supplemented with phytase. Phytase supplementation decreased InsP6-4, resulting in increased InsP3-2 and myo-inositol concentrations. Similar effects were found in ileal contents. Compared with NC, phytase supplementation resulted in greater cumulative InsP6-2 disappearance (93.6% vs. 72.8% vs. 25.0%, for NC + 2,000 FTU, NC + 500 FTU and NC, respectively, P < 0.01) till the distal ileum. Longissimus dorsi muscle plasma membrane GLUT4 concentration was increased by NC + 2,000 FTU (P < 0.01) compared with NC. In summary, high phytase supplementation increased growth performance of nursery pigs. The higher myo-inositol release from phytate could contribute to the increased expression of GLUT4 in muscle plasma membranes. Further investigation is needed to determine whether this is associated with enhanced cellular glucose uptake and utilization.


2019 ◽  
Vol 44 (11) ◽  
pp. 1180-1188 ◽  
Author(s):  
Zéphyra Appriou ◽  
Kévin Nay ◽  
Nicolas Pierre ◽  
Dany Saligaut ◽  
Luz Lefeuvre-Orfila ◽  
...  

Physical inactivity increases the risk to develop type 2 diabetes, a disease characterized by a state of insulin resistance. By promoting inflammatory state, ceramides are especially recognized to alter insulin sensitivity in skeletal muscle. The present study was designed to analyze, in mice, whether muscle ceramides contribute to physical-inactivity-induced insulin resistance. For this purpose, we used the wheel lock model to induce a sudden reduction of physical activity, in combination with myriocin treatment, an inhibitor of de novo ceramide synthesis. Mice were assigned to 3 experimental groups: voluntary wheel access group (Active), a wheel lock group (Inactive), and wheel lock group treated with myriocin (Inactive-Myr). We observed that 10 days of physical inactivity induces hyperinsulinemia and increases basal insulin resistance (HOMA-IR). The muscle ceramide content was not modified by physical inactivity and myriocin. Thus, muscle ceramides do not play a role in physical-inactivity-induced insulin resistance. In skeletal muscle, insulin-stimulated protein kinase B phosphorylation and inflammatory pathway were not affected by physical inactivity, whereas a reduction of glucose transporter type 4 content was observed. Based on these results, physical-inactivity-induced insulin resistance seems related to a reduction in glucose transporter type 4 content rather than defects in insulin signaling. We observed in inactive mice that myriocin treatment improves glucose tolerance, insulin-stimulated protein kinase B, adenosine-monophosphate-activated protein kinase activation, and glucose transporter type 4 content in skeletal muscle. Such effects occur regardless of changes in muscle ceramide content. These findings open promising research perspectives to identify new mechanisms of action for myriocin on insulin sensitivity and glucose metabolism.


2019 ◽  
Vol 316 (5) ◽  
pp. E931-E939 ◽  
Author(s):  
Jin-Ho Koh ◽  
Chad R. Hancock ◽  
Dong-Ho Han ◽  
John O. Holloszy ◽  
K. Sreekumaran Nair ◽  
...  

The objective of this study is to determine whether AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), or peroxisome proliferator-activated receptor β (PPARβ) can independently mediate the increase of glucose transporter type 4 (GLUT4) expression that occurs in response to exercise training. We found that PPARβ can regulate GLUT4 expression without PGC-1α. We also found AMPK and PPARβ are important for maintaining normal physiological levels of GLUT4 protein in the sedentary condition as well following exercise training. However, AMPK and PPARβ are not essential for the increase in GLUT4 protein expression that occurs in response to exercise training. We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. Furthermore, exercise training increases the cooperation of AMPK and PPARβ to regulate glucose uptake. In conclusion, cooperation between AMPK and PPARβ via NRF-1/MEF2A pathway enhances the exercise training mediated adaptive increase in GLUT4 expression and subsequent glucose uptake in skeletal muscle.


2018 ◽  
Vol 22 (3) ◽  
pp. 161-168 ◽  
Author(s):  
María de los Ángeles Carrasco-Ruiz ◽  
Laura G. Hernández-Aragón ◽  
Jesús Ramsés Chávez-Ríos ◽  
Jorge Rodríguez-Antolín ◽  
Pablo Pacheco ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1160 ◽  
Author(s):  
Rachel Wong ◽  
Peter Howe

Pre-clinical data and human trials indicate that resveratrol supplementation may help to counteract diabetes. Several mechanisms of action have been proposed to explain its metabolic benefits, including activation of sirtuins and estrogen receptors (ER) to promote glucose transporter type-4 (GLUT4) translocation and increase glucose uptake. Resveratrol can also enhance vasodilator function, yet the possibility that this action might help to alleviate insulin resistance in type-2 diabetes mellitus has received little attention. In this brief review we propose that, by restoring impaired endothelium-dependent vasodilatation in insulin resistant individuals resveratrol increases blood perfusion of skeletal muscle, thereby facilitating glucose delivery and utilization with resultant improvement of insulin sensitivity. Thus, circulatory improvements by vasoactive nutrients such as resveratrol may play a role in preventing or alleviating insulin resistance.


IUBMB Life ◽  
2007 ◽  
Vol 59 (3) ◽  
pp. 134-145 ◽  
Author(s):  
Seung-Soon Im ◽  
Sool-Ki Kwon ◽  
Tae-Hyun Kim ◽  
Ha-il Kim ◽  
Yong-Ho Ahn

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