Protein Synthesis Activity Research Articles

Resistance exercise: a mighty tool that adapts, destroys, rebuilds and modulates the molecular and structural environment of skeletal muscle.

Skeletal muscle regulates health and performance by maintaining or increasing strength and muscle mass. Although the molecular mechanisms in response to resistance exercise (RE) significantly target the activation of protein synthesis, a plethora of other mechanisms and structures must be involved in orchestrating the communication, repair, and restoration of homeostasis after RE stimulation. In practice, RE can be modulated by variations in intensity, continuity and volume, which affect molecular responses and skeletal muscle adaptation. Knowledge of these aspects is important with respect to planning of training programs and assessing the impact of RE training on skeletal muscle. In this narrative review, we introduce general aspects of skeletal muscle substructures that adapt in response to RE. We further highlighted the molecular mechanisms that control human skeletal muscle anabolism, degradation, repair and memory in response to acute and repeated RE and linked these aspects to major training variables. Although RE is a key stimulus for the activation of skeletal muscle anabolism, it also induces myofibrillar damage. Nevertheless, to increase muscle mass accompanied by a corresponding adaptation of the essential substructures of the sarcomeric environment, RE must be continuously repeated. This requires the permanent engagement of molecular mechanisms that re-establish skeletal muscle integrity after each RE-induced muscle damage. Various molecular regulators coordinately control the adaptation of skeletal muscle after acute and repeated RE and expand their actions far beyond muscle growth. Variations of key resistance training variables likely affect these mechanisms without affecting muscle growth.

Nitrogen sources differentially affect respiration, growth, and carbon allocation in Andean and Lowland ecotypes of Chenopodium quinoa Willd.

Chenopodium quinoa Willd. is a native species that originated in the High Andes plateau (Altiplano) and its cultivation spread out to the south of Chile. Because of the different edaphoclimatic characteristics of both regions, soils from Altiplano accumulated higher levels of nitrate () than in the south of Chile, where soils favor ammonium (NH4 +) accumulation. To elucidate whether C. quinoa ecotypes differ in several physiological and biochemical parameters related to their capacity to assimilate and NH4 +, juvenile plants of Socaire (from Altiplano) and Faro (from Lowland/South of Chile) were grown under different sources of N ( or NH4 +). Measurements of photosynthesis and foliar oxygen-isotope fractionation were carried out, together with biochemical analyses, as proxies for the analysis of plant performance or sensitivity to NH4 +. Overall, while NH4 + reduced the growth of Socaire, it induced higher biomass productivity and increased protein synthesis, oxygen consumption, and cytochrome oxidase activity in Faro. We discussed that ATP yield from respiration in Faro could promote protein production from assimilated NH4 + to benefit its growth. The characterization of this differential sensitivity of both quinoa ecotypes for NH4 + contributes to a better understanding of nutritional aspects driving plant primary productivity.

Soy-Based Tempeh Rich in Paraprobiotics Properties as Functional Sports Food: More Than a Protein Source.

To date, there has been no recent opinion that explores tempeh as a functional food that can improve sports performance. Hence, this opinion article aims to elaborate on recent findings on the potential effect on sports performance of soy-based tempeh. This opinion paper presents updated evidence based on literature reviews about soy-based tempeh and its relationship with sports performance. The paraprobiotic role of Lactobacillus gasseri for athletes has been found to restore fatigue and reduce anxiety. This is achieved by increasing protein synthesis activity in eukaryotic initiation factor-2 (EIF2) signaling known as an adaptive pathway for integrated stress response. In addition, these paraprobiotics prevent down-regulation associated with the oxidative phosphorylation gene, thereby contributing to the maintenance of mitochondrial function and recovery from fatigue. The authors believe that this opinion article will encourage researchers to continue to evolve soybean-based tempeh food products and increase the performance of athletes by consuming soy-based foods.

Seed Germination and Vegetative Growth of Petunia (Petunia hybrida) Genotypes to Salt Stress

Salinity is a brutal threat to sustainability of crop production and exhibits injurious effect on major plant processes including protein synthesis, cell division and photosynthetic activity. Germination and early growth of plants are most susceptible to salinity effect in comparison to other growth stages. In this context, the seed emergence and early vegetative growth of flowers needs to be tested properly. The pot based study was conducted in Completely Randomized Design (CRD) with three replicates at Sindh Agriculture University Tandojam. The goal of this investigation was to explore the performance of petunia plants to salt stress environment at early growth stage. Two petunia varieties (V1= Prism blue, V2= Hala lop petunia rose) were evaluated against six levels of salt stress (T1 = Canal irrigation water [Control], T2 = 3 dS m-1, T3 = 5 dS m-1, T4 = 7 dS m-1, T5 = 9 dS m-1, T6 = 11 dS m-1).The results showed that there was an inverse effect of salt stress on all the traits examined and with each increased level of salinity in irrigation water; the values of petunia plant traits were significantly decreased. The petunia grown in pots given only canal water (control) revealed better performance for germination and growth attributes. It was further noted that that salt stress up to 3 dS m-1 level was generally tolerated by petunia. Among petunia varieties, Hala lop petunia rose performance was better and showed relative tolerance to salt stress over Prism blue, but in most cases the differences were insignificant (P>0.05).

Biphasic scaffolds of polyvinyl alcohol/gelatin reinforced with polycaprolactone as biomedical materials supporting for bone augmentation based on anatomical mimicking; fabrication, characterization, physical and mechanical properties, and in vitro testing

Reinforced biphasic scaffolds were fabricated with based materials design of anatomical mimicking and evaluated to identify the certain application for maxillofacial surgery. The scaffolds created the polyvinyl alcohol (PVA) with a percentage of gelatin of 5% and were coated with polycaprolactone (PCL) that a different number of cycles 0, 1, 5, 10, and 15 cycles (PCL0, PCL1, PCL5, PCL10, and PCL15 were used to fabricate biphasic scaffolds via bubbling and freeze-thawing before reinforce with immersion coating techniques. The structure and morphology of the scaffolds were characterized and observed by a scanning electron microscope, a differential scanning calorimeter, and a thermogravimetric analyzer, respectively. The performance of the scaffolds was tested in terms of their swelling behavior, degradation, and mechanical properties. They were cultured with MC3T3E1 osteoblast cells and L929 fibroblast cells. The main biological performance of cell proliferation was analyzed, and protein synthesis, calcium synthesis, and alkaline phosphatase activity of the scaffolds were studied. Their morphology demonstrated fewer pores when coated with PCL. Mechanical strength of the modified scaffolds increased followed by the cycles of coating with PCL. The scaffolds with more cycle of PCL coating lower swelling and degradability than without PCL coating. They had more thermal stability than the scaffold without PCL coating. The scaffolds with PCL coating demonstrated better bio-functionality to activate cell response than without coating. Finally, the result exhibited that PCL10 provide a suitably reinforced biphasic scaffold with high promise for maxillofacial surgery.

Derivation of Human Corneal Keratocytes from ReLEx SMILE Lenticules for Cell Therapy and Tissue Engineering.

Fibroblasts isolated and expanded from ReLEx SMILE lenticules can be a source of human keratocytes. Since corneal keratocytes are quiescent cells, it is difficult to expand them in vitro in suitable numbers for clinical and experimental use. In the present study, this problem was solved by isolating and growing corneal fibroblasts (CFs) with a high proliferative potential and their reversion to keratocytes in a selective serum-free medium. Fibroblasts reversed into keratocytes (rCFs) had a dendritic morphology and ultrastructural signs of activation of protein synthesis and metabolism. The cultivation of CFs in a medium with 10% FCS and their reversion into keratocytes was not accompanied by the induction of myofibroblasts. After reversion, the cells spontaneously formed spheroids and expressed keratocan and lumican markers, but not mesenchymal ones. The rCFs had low proliferative and migratory activity, and their conditioned medium contained a low level of VEGF. CF reversion was not accompanied by a change with the levels of IGF-1, TNF-alpha, SDF-1a, and sICAM-1. In the present study, it has been demonstrated that fibroblasts from ReLEx SMILE lenticules reverse into keratocytes in serum-free KGM, maintaining the morphology and functional properties of primary keratocytes. These keratocytes have a potential for tissue engineering and cell therapy of various corneal pathologies.

SRC2 controls CD4+ T cell activation via stimulating c-Myc-mediated upregulation of amino acid transporter Slc7a5

Tcell activation stimulates substantially increased protein synthesis activity to accumulate sufficient biomass for cell proliferation. The protein synthesis is fueled by the amino acids transported from the environment. Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. Here, we show that SRC2 recruited by c-Myc enhances CD4+ Tcell activation to stimulate immune responses via upregulation of amino acid transporter Slc7a5. Mice deficient of SRC2 in Tcells (SRC2fl/fl/CD4Cre) are resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and susceptible to Citrobacter rodentium (C.rodentium)infection. Adoptive transfer of naive CD4+ Tcells from SRC2fl/fl/CD4Cre mice fails to elicit EAE and colitis in Rag1/recipients. Further, CD4+ Tcells from SRC2fl/fl/CD4Cre mice display defective Tcell proliferation, cytokine production, and differentiation both invitro and invivo. Mechanically, SRC2 functions as a coactivator to work together with c-Myc to stimulate the expression of amino acid transporter Slc7a5 required for Tcell activation. Slc7a5 fails to be up-regulated in CD4+ Tcells from SRC2fl/fl/CD4Cre mice, and forced expression of Slc7a5 rescues proliferation, cytokine production, and the ability of SRC2fl/fl/CD4Cre CD4+ Tcells to induce EAE. Therefore, SRC2 is essential for CD4+ Tcell activation and, thus, a potential drug target for controlling CD4+ Tcell-mediated autoimmunity.

The microalgae-based wastewater treatment system coupled with Cerium: A potential way for energy saving and microalgae boost.

The microalgae-based system attracts more attention in wastewater treatment for high quality effluent, low carbon emission, and resource utilization. Light is the key factor for algae growth, but the light masking in sewage will cause low efficiency of the system. This study designed laboratory scale experiments with Chlorella to investigate the influence of cerium on the nutrient removal by algae wastewater treatment system under different light intensities. The best removal rates of NH4-N, TP, and COD were 72.43%, 88.87%, and 68.08% under 50µmol/(m 2·s) light intensity and 1mg/L Ce. Low concentration of Ce could activate protein synthesis, electron transfer, and antioxidase, while excessive Ce might cause toxicity which could be relieved by strong light for energy supply and further activating superoxide dismutase (SOD) and catalase (CAT). Comparing to other similar experiences, this system reached an equal or greater performance on nutrients removal with better efficiency in light utilization. It might provide a new idea for microalgae-based system development.

Protective effects of methylsulfonylmethane (MSM) on barrier function injury of porcine intestinal epithelial cells (IPEC-J2) induced by lipopolysaccharide (LPS)

Methylsulfonylmethane (MSM) is a natural organic sulfur component that has anti-inflammatory and antioxidant properties. In this study, injury of porcine intestinal epithelial cell (IPEC-J2) models were used to investigate the effect of MSM on lipopolysaccharide (LPS)-induced porcine intestinal epithelium barrier damage. The results of the cell cycle showed that the cells in the G2/M phase decreased significantly with the supplementation of 300 mmol/L MSM ( P < 0.05). The ELISA assay revealed that MSM could significantly inhibit the expression of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 ( P < 0.01). Meanwhile, MSM could significantly increase the value of cell monolayer transepithelial electrical resistance while reducing the FITC-dextran flux permeability and lactate dehydrogenase activity in IPEC-J2 cells ( P < 0.01). Additionally, 300 mmol/L MSM significantly increased both mRNA and protein expression of occludin, claudin-1, and ZO-1 ( P < 0.05). Furthermore, MSM prevented the downregulation of epidermal growth factor receptor (EGFR) by LPS, indicating that MSM might enhance tight junction function through mechanisms of activation of EGFR-mediated protein synthesis in IPEC-J2 cells. Therefore, our findings suggested that MSM has protective effects on inflammation and epithelial barrier injury in LPS-induced IPEC-J2 cells, indicating that MSM might be used as a potential therapeutic agent in the pig industry.

Accumulation of cyanobacterial photosystem II containing the "rogue" D1 subunit is controlled by FtsH protease and the synthesis of the standard D1 protein.

Unicellular diazotrophic cyanobacteria contribute significantly to the photosynthetic productivity of the ocean and the fixation of molecular nitrogen, with photosynthesis occurring during the day and nitrogen fixation during the night. In species like Crocosphaera watsonii WH8501 the decline in photosynthetic activity in the night is accompanied by the disassembly of oxygen-evolving photosystem II (PSII) complexes. Moreover, in the second half of the night phase a small amount of rogue D1 (rD1), which is related to the standard form of D1 subunit found in oxygen-evolving PSII, but of unknown function, accumulates but is quickly degraded at the start of the light phase. We show here that removal of rD1 is independent of rD1 transcript level, thylakoid redox state and trans-thylakoidal pH but requires light and active protein synthesis. We also found that the maximal level of rD1 positively correlates with the maximal level of chlorophyll biosynthesis precursors and enzymes, which suggests a possible role for rPSII in the activation of chlorophyll biosynthesis just before or upon the onset of light, when new photosystems are synthesized. By studying strains of Synechocystis PCC 6803 expressing Crocosphaera rD1 we found that accumulation of rD1 is controlled by the light-dependent synthesis of the standard D1 protein which triggers the fast FtsH2-dependent degradation of rD1. Affinity purification of FLAG-tagged rD1 unequivocally demonstrated the incorporation of rD1 into a non-oxygen-evolving PSII complex which we term rogue PSII (rPSII). The complex lacks the extrinsic proteins stabilizing the oxygen-evolving Mn4CaO5 cluster but contains the Psb27 and Psb28-1 assembly factors.

Side-by-Side Profiling of Oxazolidinones to Estimate the Therapeutic Window against Mycobacterial Infections.

New oxazolidinones are in clinical development for the treatment of tuberculosis and nontuberculous mycobacterial (NTM) infections, as a replacement for linezolid and tedizolid, which cause mitochondrial toxicity after prolonged treatment. Here, we carried out side-by-side measurements of mitochondrial protein synthesis inhibition and activity against clinically relevant mycobacterial pathogens of approved and novel oxazolidinones. We found a large range of selectivity indices suggesting TBI-223 and sutezolid as promising candidates against tuberculosis and NTM lung disease caused by Mycobacterium kansasii.

Regulation of germline proteostasis by HSF1 and insulin/IGF-1 signaling.

Protein homeostasis (proteostasis) is essential for cellular function and organismal health and requires the concerted actions of protein synthesis, folding, transport, and turnover. In sexually reproducing organisms, the immortal germline lineage passes genetic information across generations. Accumulating evidence indicates the importance of proteome integrity for germ cells as genome stability. As gametogenesis involves very active protein synthesis and is highly energy-demanding, it has unique requirements for proteostasis regulation and is sensitive to stress and nutrient availability. The heat shock factor 1 (HSF1), a key transcriptional regulator of cellular response to cytosolic and nuclear protein misfolding has evolutionarily conserved roles in germline development. Similarly, insulin/insulin-like growth factor-1 (IGF-1) signaling, a major nutrient-sensing pathway, impacts many aspects of gametogenesis. Here, we focus on HSF1 and IIS to review insights into their roles in germline proteostasis and discuss the implications on gamete quality control during stress and aging.

The skeletal muscle fiber periphery: A nexus of mTOR-related anabolism.

Skeletal muscle anabolism is driven by numerous stimuli such as growth factors, nutrients (i.e., amino acids, glucose), and mechanical stress. These stimuli are integrated by the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signal transduction cascade. In recent years, work from our laboratory and elsewhere has sought to unravel the molecular mechanisms underpinning the mTOR-related activation of muscle protein synthesis (MPS), as well as the spatial regulation of these mechanisms within the skeletal muscle cell. These studies have suggested that the skeletal muscle fiber periphery is a region of central importance in anabolism (i.e., growth/MPS). Indeed, the fiber periphery is replete with the substrates, molecular machinery, and translational apparatus necessary to facilitate MPS. This review provides a summary of the mechanisms underpinning the mTOR-associated activation of MPS from cell, rodent, and human studies. It also presents an overview of the spatial regulation of mTORC1 in response to anabolic stimuli and outlines the factors that distinguish the periphery of the cell as a highly notable region of skeletal muscle for the induction of MPS. Future research should seek to further explore the nutrient-induced activation of mTORC1 at the periphery of skeletal muscle fibers.

Current Worldwide Trends in Pediatric Helicobacter pylori Antimicrobial Resistance.

Helicobacter pylori (H. pylori) has acquired several resistance mechanisms in order to escape the currently used eradication regimens such as mutations that impair the replication, recombination, and transcription of DNA; the antibiotics capability to interact with protein synthesis and ribosomal activity; the adequate redox state of bacterial cells; or the penicillin-binding proteins. The aim of this review was to identify the differences in pediatric H. pylori antimicrobial-resistance trends between continents and countries of the same continent. In Asian pediatric patients, the greatest antimicrobial resistance was found to metronidazole (>50%), probably due to its wide use for parasitic infections. Aside from the increased resistance to metronidazole, the reports from different Asian countries indicated also high resistance rates to clarithromycin, suggesting that ciprofloxacin-based eradication therapy and bismuth-based quadruple therapy might be optimal choices for the eradication of H. pylori in Asian pediatric population. The scarce evidence for America revealed that H. pylori strains display an increased resistance to clarithromycin (up to 79.6%), but not all studies agreed on this statement. Pediatric patients from Africa also presented the greatest resistance rate to metronidazole (91%), but the results in terms of amoxicillin remain contradictory. Nevertheless, the lowest resistance rates in most of the African studies were found for quinolones. Among European children, the most frequent antimicrobial resistance was also noticed for metronidazole and clarithromycin (up to 59% and 45%) but with a predominance for clarithromycin as compared to other continents. The differences in antibiotic use among continents and countries worldwide is clearly responsible for the discrepancies regarding H. pylori antimicrobial-resistance patterns, emphasizing the crucial role of global judicious antibiotic use in order to control the increasing resistance rates worldwide.

Age-related ultrastructural changes in spheroids of the adipose-derived multipotent mesenchymal stromal cells from ovariectomized mice.

Introduction: Adipose-derived multipotent mesenchymal stromal cells (ADSCs) are widely used for cell therapy, in particular for the treatment of diseases of the nervous system. An important issue is to predict the effectiveness and safety of such cell transplants, considering disorders of adipose tissue under age-related dysfunction of sex hormones production. The study aimed to investigate the ultrastructural characteristics of 3D spheroids formed by ADSCs of ovariectomized mice of different ages compared to age-matched controls. Methods: ADSCs were obtained from female CBA/Ca mice randomly divided into four groups: CtrlY-control young (2 months) mice, CtrlO-control old (14 months) mice, OVxY-ovariectomized young mice, and OVxO-ovariectomized old mice of the same age. 3D spheroids were formed by micromass technique for 12-14 days and their ultrastructural characteristics were estimated by transmission electron microscopy. Results and Discussion: The electron microscopy analysis of spheroids from CtrlY animals revealed that ADSCs formed a culture of more or less homogeneous in size multicellular structures. The cytoplasm of these ADSCs had a granular appearance due to being rich in free ribosomes and polysomes, indicating active protein synthesis. Extended electron-dense mitochondria with a regular cristae structure and a predominant condensed matrix were observed in ADSCs from CtrlY group, which could indicate high respiratory activity. At the same time, ADSCs from CtrlO group formed a culture of heterogeneous in size spheroids. In ADSCs from CtrlO group, the mitochondrial population was heterogeneous, a significant part was represented by more round structures. This may indicate an increase in mitochondrial fission and/or an impairment of the fusion. Significantly fewer polysomes were observed in the cytoplasm of ADSCs from CtrlO group, indicating low protein synthetic activity. The cytoplasm of ADSCs in spheroids from old mice had significantly increased amounts of lipid droplets compared to cells obtained from young animals. Also, an increase in the number of lipid droplets in the cytoplasm of ADSCs was observed in both the group of young and old ovariectomized mice compared with control animals of the same age. Together, our data indicate the negative impact of aging on the ultrastructural characteristics of 3D spheroids formed by ADSCs. Our findings are particularly promising in the context of potential therapeutic applications of ADSCs for the treatment of diseases of the nervous system.

Roles of the cumulus-oocyte transzonal network and the Fragile X protein family in oocyte competence.

RNA granules travel through the cumulus cell network of transzonal projections which is associated with oocyte developmental competence, and RNA packaging involves RNA-binding proteins of the Fragile X protein family. The determinants of oocyte developmental competence have puzzled scientists for decades. It is known that follicular conditions can nurture the production of a high-quality oocyte, but the underlying mechanisms remain unknown. Somatic cumulus cells most proximal to the oocyte are known to have cellular extensions that reach across the zona pellucida and contact with the oocyte plasma membrane. Herein, it was found that transzonal projections (TZPs) network quality is associated with developmental competence. Knowing that ribonucleoparticles are abundant within TZPs, the distribution of RNA-binding proteins was studied. The Fragile X-related proteins (FXR1P and FXR2P) and two partnering protein families, namely cytoplasmic FMRP-interacting protein and nuclear FMRP-interacting protein, exhibited distinctive patterns consistent with roles in regulating mRNA packaging, transport, and translation. The expression of green fluorescent protein (GFP)-FMRP fusion protein in cumulus cells showed active granule formation and their transport and transfer through filipodia connecting with neighboring cells. Near the projections' ends was found the cytoskeletal anchoring protein Filamin A and active protein synthesis sites. This study highlights key proteins involved in delivering mRNA to the oocyte. Thus, cumulus cells appear to indeed support the development of high-quality oocytes via the transzonal network.

Physical Activity Increases Immunity to COVID-19 Infection.

Coronavirus are truly one of the maximum critical fantastic-stranded non-segmented RNA viruses, named after the approximately 126-nm-diameter envelope around the nucleic acid-protein complicated. The virus causes significant harm to human fitness, including direct injury to the respiratory system, immune system compromise, worsening of the underlying clinical conditions, and eventually systemic failure and death. Exercise affects the immune system's antiviral mechanisms. Modest exercise, done before or after infection, improves morbidity and mortality to the contamination, according to animal investigations using influenza and simplex virus in the respiratory tract. Moreover, preclinical research has demonstrated that overtraining has a negative impact on the body's response to viral infections. Follow-up research has shed some light on the mechanisms underlying these discoveries. Through the activation of muscle protein synthesis, physical activity (PA) and exercise are essential for maintaining muscle mass. On the other hand, a lack of muscle contractile activity throughout the country of no exercise, particularly in elderly people, is a major contributor to anabolic rigidity and muscle atrophy.

Drinking Mineral Water and Low-Intensity Electromagnetic Radiation Combinational Effect on Rat Testes in Metabolic Syndrome: а Randomized Controlled Study

INTRODUCTION. To correct disorders in the male reproductive system organs in the metabolic syndrome, it seems reasonable to use a combined effect of natural and artificial therapeutic physical factors – drinking mineral water and low-intensity electromagnetic interference of ultrahigh frequency – on an experimental model of this disease. These factors have antioxidant, cytoprotective and regenerative effects and can have a wide range of effects on various adaptation and protective regulatory mechanisms. AIM. To reveal the development of metabolic and structural adaptation-protective reactions in rat testes under the combined effect of drinking sulphate mineral water and low-intensity electromagnetic radiation microwave in experimental simulation of metabolic syndrome. MATERIAL AND METHODS. The experiments were performed on 26 nonlinear male rats weighing 180-200g. The metabolic syndrome model was reproduced for 60 days using a high-caloric diet. The rats were divided into 3 groups: 1st (experimental)-rats received drinking sulfate mineral water in combination with microwave electromagnetic radiation against the background of a high-calorie diet; 2nd (control) – rats received only a high-calorie diet; 3rd (intact) – rats without any influences. Research methods: biochemical, lightoptical, morphometric, electron microscopy. Significance of differences was assessed by Student's t-test. RESULTS AND DISCUSSION. It was found that the combinational effect of drinking sulfate mineral water and low-intensity electromagnetic radiation microwave contributed to the enhancement of a number of adaptive and protective reactions in the testes of rats against the background of a high-caloric diet. They were mainly manifested in the activation of antioxidant protection and protein synthesis, improvement of spermatogenic cells differentiation processes and increase in their number, enhancement of cellular and intracellular regeneration. CONCLUSION. The data obtained can be used in the development of new approaches to the methods of adaptation-protective and compensatory-restorative processes enhancement in the organs of the male reproductive system in metabolic syndrome.

Branched-Chain Amino Acids and Insulin Resistance, from Protein Supply to Diet-Induced Obesity.

For more than a decade, there has been a wide debate about the branched-chain amino acids (BCAA) leucine, valine, and isoleucine, with, on the one hand, the supporters of their anabolic effects and, on the other hand, those who suspect them of promoting insulin resistance. Indeed, the role of leucine in the postprandial activation of protein synthesis has been clearly established, even though supplementation studies aimed at taking advantage of this property are rather disappointing. Furthermore, there is ample evidence of an association between the elevation of their plasma concentrations and insulin resistance or the risk of developing type 2 diabetes, although there are many confounding factors, starting with the level of animal protein consumption. After a summary of their metabolism and anabolic properties, we analyze in this review the factors likely to increase the plasma concentrations of BCAAs, including insulin-resistance. After an analysis of supplementation or restriction studies in search of a direct role of BCAAs in insulin resistance, we discuss an indirect role through some of their metabolites: branched-chain keto acids, C3 and C5 acylcarnitines, and hydroxyisobutyrate. Overall, given the importance of insulin in the metabolism of these amino acids, it is very likely that small alterations in insulin sensitivity are responsible for a reduction in their catabolism long before the onset of impaired glucose tolerance.

Replication Activities of Major 5' Terminally Deleted Group-B Coxsackievirus RNA Forms Decrease PCSK2 mRNA Expression Impairing Insulin Maturation in Pancreatic Beta Cells.

Emergence of 5' terminally deleted coxsackievirus-B RNA forms (CVB-TD) have been associated with the development of human diseases. These CVB-TD RNA forms have been detected in mouse pancreas during acute or persistent experimental infections. To date, the impact of the replication activities of CVB-TD RNA forms on insulin metabolism remains unexplored. Using an immunocompetent mouse model of CVB3/28 infection, acute and persistent infections of major CVB-TD populations were evidenced in the pancreas. The inoculation of mice with homogenized pancreases containing major CVB-TD populations induced acute and chronic pancreatic infections with pancreatitis. In the mouse pancreas, viral capsid protein 1 (VP1) expression colocalized with a decrease in beta cells insulin content. Moreover, in infected mouse pancreases, we showed a decrease in pro-hormone convertase 2 (PCSK2) mRNA, associated with a decrease in insulin plasmatic concentration. Finally, transfection of synthetic CVB-TD50 RNA forms into cultured rodent pancreatic beta cells demonstrated that viral replication with protein synthesis activities decreased the PCSK2 mRNA expression levels, impairing insulin secretion. In conclusion, our results show that the emergence and maintenance of major CVB-TD RNA replicative forms in pancreatic beta cells can play a direct, key role in the pathophysiological mechanisms leading to the development of type 1 diabetes.