scholarly journals Designed Functional Dispersion for Insulin Protection from Pepsin Degradation and Skeletal Muscle Cell Proliferation: In Silico and In Vitro Study

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 852 ◽  
Author(s):  
Veera Chittepu ◽  
Poonam Kalhotra ◽  
Tzayhri Gallardo-Velázquez ◽  
Raúl Robles-de la Torre ◽  
Guillermo Osorio-Revilla

Functionalized single-walled carbon nanotubes with polyethylene glycol (PEGylated SWCNTs) are a promising nanomaterial that recently has emerged as the most attractive “cargo” to deliver chemicals, peptides, DNA and RNAs into cells. Insulin therapy is a recommended therapy to treat diabetes mellitus despite its side effects. Recently, functional dispersion made up of bioactive peptides, bioactive compounds and functionalized carbon nanomaterials such as PEGylated SWCNTs have proved to possess promising applications in nanomedicine. In the present study, molecular modeling simulations are utilized to assist in designing insulin hormone-PEGylated SWCNT composites, also called functional dispersion; to achieve this experimentally, an ultrasonication tool was utilized. Enzymatic degradation assay revealed that the designed functional dispersion protects about 70% of free insulin from pepsin. In addition, sulforhodamine B (SRB) assay, the quantification of insulin and glucose levels in differentiated skeletal muscle cell supernatants, reveals that functional dispersion regulates glucose and insulin levels to promote skeletal muscle cell proliferation. These findings offer new perspectives for designed functional dispersion, as potential pharmaceutical preparations to improve insulin therapy and promote skeletal muscle cell health.

2013 ◽  
Vol 304 (1) ◽  
pp. C56-C67 ◽  
Author(s):  
James F. Markworth ◽  
David Cameron-Smith

Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro . C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF2α and PGE2; however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Katherine E LaBarbera ◽  
Kevin S O'Fallon ◽  
Priscilla M Clarkson ◽  
Sarah Witkowski

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 305
Author(s):  
Poonam Kalhotra ◽  
Veera C.S.R. Chittepu ◽  
Guillermo Osorio-Revilla ◽  
Tzayhri Gallardo-Velazquez

Diabetes mellitus is a severe health problem in Mexico, and its prevalence is increasing exponentially every year. Recently, DPP-4 (dipeptidyl peptidase-4) inhibitors have become attractive oral anti-hyperglycemic agents to reduce the pathology of diabetes. Gliptin’s family, such as sitagliptin, vildagliptin, and alogliptin, are in clinical use to treat diabetes mellitus but possess side effects. Therefore, there is a specific need to look for new therapeutic scaffolds (biomolecules). Garlic bulb is widely used as a traditional remedy for the treatment of diabetes. The garlic extracts are scientifically proven to control glucose levels in patients with diabetes, despite the unknown mechanism of action. The aim of the study is to investigate the antidiabetic effects of ultrasonication assisted garlic bulb extract. To achieve this, in-vitro assays such as DPP-4 inhibitory and antioxidant activities were investigated. Further, functional group analysis using FTIR and identification of phytochemicals using mass spectrometry analysis was performed. The results showed that 70.9 µg/mL of garlic bulb extract inhibited 50% DPP-4 activity. On top of that, the garlic extract exhibited a 20% scavenging activity, equivalent to 10 µg/mL of ascorbic acid. Molecular docking simulations on identified phytochemicals using mass spectrometry revealed their potential binding at the DPP-4 druggable region, and therefore the possible DPP-4 inhibition mechanism. These results suggest that prepared garlic extract contains phytochemicals that inhibit DPP-4 and have antioxidant activity. Also, the prepared extract induces skeletal muscle cell proliferation that demonstrates the antidiabetic effect and its possible mechanism of action.


2019 ◽  
Vol 03 (04) ◽  
pp. 267 ◽  
Author(s):  
M. Battistelli ◽  
S. Salucci ◽  
S. Burattini ◽  
E. Falcieri

2013 ◽  
Vol 48 (3) ◽  
pp. 403-414 ◽  
Author(s):  
Elise Duchesne ◽  
Patrice Bouchard ◽  
Marie-Pier Roussel ◽  
Claude H. Côté

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