Carnosol Increases Skeletal Muscle Cell Glucose Uptake via AMPK-Dependent GLUT4 Glucose Transporter Translocation

Vlavcheski, Filip; Baron, David C.; Vlachogiannis, Ioannis; MacPherson, Rebecca E. K.; Tsiani, Evangelia

doi:10.3390/ijms19051321

Cited by 45 publications

(36 citation statements)

References 58 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It exhibits antihyperglycemic, antioxidant, and antiobesity effects potentially via PI3K/AKT/GLUT4 signaling [66]. Also, carnosol, a compound found in spices such as sage or rosemary, increases glucose uptake via GLUT4 [67]. Interestingly, it has been proven that 1,25-dihydroxyvitamin D3 (active form of vitamin D3), which is mainly provided with food, can improve glucose uptake and has a potential in acting as an anti-inflammatory factor [68].…”

Section: Insulin-sensitizing Factorsmentioning

confidence: 99%

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Świderska¹,

Strycharz²,

Wróblewski³

et al. 2020

Blood Glucose Levels

View full text Add to dashboard Cite

Glucose uptake is regulated by several mechanisms, where insulin plays the most prominent role. This powerful anabolic hormone regulates the transport of glucose into the cell through translocation of glucose transporter from an intracellular pool to the plasma membrane mainly in metabolically active tissues like skeletal muscles, adipose tissue, or liver (GLUT4). This translocation occurs through multiple steps of PI3K/AKT signaling pathway. In this chapter, we will focus on molecular events leading to GLUT4 translocation, starting with activation of insulin receptors through signaling cascade involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) and finally, the action of their effectors. We will present regulatory mechanisms and modulators of insulin-mediated glucose uptake.

show abstract

Section: Insulin-sensitizing Factorsmentioning

confidence: 99%

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Świderska¹,

Strycharz²,

Wróblewski³

et al. 2020

Blood Glucose Levels

View full text Add to dashboard Cite

show abstract

“…Conversely, a pathological hypertrophic condition links a GLUT4 depletion, resulting in a direct increase in GLUT1 levels ( Slot et al, 1991 ; Abel et al, 1999 ; Paternostro et al, 1999 ; Tian et al, 2001 ; Kolwicz and Tian, 2011 ; Shao and Tian, 2015 ). PI3K activation appears to be necessary for GLUT4 translocation in the heart, being insulin stimulated GLUT4 translocation blocked by PI3K inhibitor ( Egert et al, 1997 ; Vlavcheski et al, 2018 ). In line with these evidences, our results furtherly showed that PI3K inactivation induced by high glucose exposure in H9c2 cells lead to a significant increased plasma membrane GLUT1/GLUT4 ratio compared to cells exposed to high glucose.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, it has been investigated the phosphoinositide 3-kinase (PIK3) activity as a possible intracellular target of the MC5R stimulation. PI3K is a major player for mediating cardiac glucose since it is a regulator of glucose transporters ( Egert et al, 1997 ; Vlavcheski et al, 2018 ), it is involved in reduction of cardiac hypertrophy ( Weeks et al, 2017 ), and it is stimulated by the MC5R after α-MSH activation in HEK293 cells ( Rodrigues et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

The Melanocortin MC5R as a New Target for Treatment of High Glucose-Induced Hypertrophy of the Cardiac H9c2 Cells

et al. 2018

View full text Add to dashboard Cite

The study explored the anti-hypertrophic effect of the melanocortin MC5R stimulation in H9c2 cardiac myocytes exposed to high glucose. This has been done by using α-MSH and selective MC5R agonists and assessing the expression of GLUT4 and GLUT1 transporters, miR-133 and urotensin receptor levels as a marker of cardiac hypertrophy. The study shows for the first time an up-regulation of MC5R expression levels in H9c2 cardiomyocytes exposed to high glucose medium (33 mM D-glucose) for 48 h, compared to cells grown in normal glucose medium (5.5 mM D-glucose). Moreover, H9c2 cells exposed to high glucose showed a significant reduction in cell viability (-40%), a significant increase in total protein per cell number (+109%), and an increase of the urotensin receptor expression levels as an evidence of cells hypertrophy. The pharmacological stimulation of MC5R with α-MSH (90 pM)of the high glucose exposed H9c2 cells increased the cell survival (+50,8%) and reduced the total protein per cell number (-28,2%) with respect to high glucose alone, confirming a reduction of the hypertrophic state as per cell area measurement. Similarly, PG-901 (selective agonist, 10-10 M) significantly increased cell viability (+61,0 %) and reduced total protein per cell number (-40,2%), compared to cells exposed to high glucose alone. Interestingly, the MC5R agonist reduced the GLUT1/GLUT4 glucose transporters ratio on the cell membranes exhibited by the hypertrophic H9c2 cells and increased the intracellular PI3K activity, mediated by a decrease of the levels of the miRNA miR-133a. The beneficial effects of MC5R agonism on the cardiac hypertrophy caused by high glucose was also observed also by echocardiographic evaluations of rats made diabetics with streptozotocin (65 mg/kg i.p.). Therefore, the melanocortin MC5R could be a new target for the treatment of high glucose-induced hypertrophy of the cardiac H9c2 cells.

show abstract

“…In addition, Oleanolic acid ( 7 ) and its derivatives have also been reported to up-regulate the expression of GLUT4, which increases the glucose-uptake activity in adipose and muscle cell lines [ 14 , 15 ]. Carnosic acid and carnosol also activate Akt and AMPKα signaling and then enhance glucose uptake in L6 myotubes as well as stimulate glucose uptake in L6 myotubes [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Glucose-Uptake Activity and Cytotoxicity of Diterpenes and Triterpenes Isolated from Lamiaceae Plant Species

et al. 2020

View full text Add to dashboard Cite

The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rates of morbidity and mortality around the world in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristics of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species: namely, Salvia africana-lutea, Leonotis ocymifolia, and Plectranthus madagascariensis, for their glucose-uptake ability. Methanolic extracts were produced from the aerial parts of each plant. Compounds were identified using different spectroscopic techniques. The glucose-uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay. Chromatographic purification of the three plant species yielded sixteen pure terpenoids. Compounds 1 (p = 0.0031), 8 (p = 0.0053), and 6 (p = 0.0086) showed a marked increase in glucose uptake, respectively. Additionally, 1, 4, and 6 exhibited cytotoxicity toward mammalian tissue with a decrease in cell viability of ~70%, ~68%, and ~67%, respectively. The results suggested that several compounds demonstrated a marked increase in glucose uptake, while two of the compounds exhibited signs of cytotoxicity. It may, therefore, be suggested that these compounds be considered as potential candidates for novel plant-derived alternative therapies in the treatment of type 2 diabetes.

show abstract

Carnosol Increases Skeletal Muscle Cell Glucose Uptake via AMPK-Dependent GLUT4 Glucose Transporter Translocation

Cited by 45 publications

References 58 publications

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

The Melanocortin MC5R as a New Target for Treatment of High Glucose-Induced Hypertrophy of the Cardiac H9c2 Cells

Glucose-Uptake Activity and Cytotoxicity of Diterpenes and Triterpenes Isolated from Lamiaceae Plant Species

Contact Info

Product

Resources

About