Co-ingestion of glutamine and leucine synergistically promotes mTORC1 activation

Yoshimura, Ryoji; Nomura, Shuichi

doi:10.1038/s41598-022-20251-2

“…To support this notion, synergistic promotive effect of Gln on Leu-mediated mTORC1 activation has been reported. 18 STZ-HFD-Cltrn1/y demonstrated the increased phosphorylation of mTOR, and we observed reversed activation of mTOR in STZ-HFD-Cltrn2/y associated with increased AAs excretion into urine. We further investigated the status of autophagy downstream of mTORC1 in the kidney tissues.…”

Section: Discussionmentioning

confidence: 48%

“…To support this notion, synergistic promotive effect of Gln on Leu-mediated mTORC1 activation has been reported. 18 …”

Section: Discussionmentioning

confidence: 99%

Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes

Kano,

Yamaguchi,

Mise

et al. 2023

Kidney360

0

View full text Add to dashboard Cite

Background: Inhibition of glucose influx into proximal tubular cells (PTCs) by sodium-glucose co-transporter 2 (SGLT2) inhibitors revealed prominent therapeutic impacts on diabetic kidney disease (DKD). Collectrin (CLTRN) serves as a chaperone for the trafficking of neutral amino acid transporters in the apical membranes of proximal tubular cells. We investigated the beneficial effects of reduced influx of amino acids into proximal tubular cells in diabetes and obesity model of Cltrn-/y mice. Methods: Cltrn+/y and Cltrn-/y mice at 5 weeks of age were assigned to standard diet- (STD) and streptozotocin and high fat diet-treated (STZ-HFD) groups. Results: At 22-23 weeks of age, body weight and HbA1c levels significantly increased in STZ-HFD-Cltrn+/y compared to STD-Cltrn+/y; however, they were not altered in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. At 20 weeks of age, urinary albumin creatinine ratio (UACR) was significantly reduced in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. Under the treatments with STZ and HFD, the Cltrn gene deficiency caused significant increase in urinary concentration of amino acids such as Gln, His, Gly, Thr, Tyr, Val, Trp, Phe, Ile, Leu and Pro. In proximal tubular cells in STZ-HFD-Cltrn+/y, the enlarged lysosomes with diameter of 10 μm or more were associated with reduced autolysosomes, and the formation of giant lysosomes was prominently suppressed in STZ-HFD-Cltrn-/y. Phospho-mTOR and inactive form of phospho-TFEB were reduced in STZ-HFD-Cltrn-/y compared to STZ-HFD-Cltrn+/y. Conclusions: The reduction of amino acids influx into proximal tubular cells inactivated mTOR, activated TFEB, improved lysosome function, and ameliorated vacuolar formation of PTCs in STZ-HFD-Cltrn-/y mice.

show abstract

“…That the myocardial protection from oxygen glucose deprivation/ re-oxygenation-induced oxidative injury runs by Nrf2 through activating Ang2-AT2 and VEGF-A for activating heme oxygenase and heme Biosynthesis through running anti-inflammatory growth, where NO and NO donors (NO mechanism) serve as a signaling molecule in the modulating tissue stress response and protect tissue from oxygen glucose deprivation. Furthermore, Grape seed proanthocyanidin extract (GSPE) showed neuroprotective effects on the bladder of diabetic rats, as shown by the increased expression of nerve growth factor (NGF) and decreased expression of the precursor of nerve growth factor (proNGF) [54]. It's clear that Grape seed proanthocyanidin extract "GSPE" contains enough necessary amino acids as Glu, tryptophan, Thr, Ser which are having the roles of reactivating pyrimidine and purines kinases which are necessary for reactivating Estrogen productions from estradiol (from pro-inflammation and accumulated cholesterol) followed by activating glucocorticoidbeta and B-arrestins synthesis where GCs-beta begin to promote both mineralocorticoid and followed by B Adrenergic production which will activate Nrf2 synthesis for activating both Ang2-AT2 and VEGF-A synthesis which activate NGF with adoption to antioxidative functional activity with the concomitant adopting the elevation of downstream hemeoxygenase-1 (HO-1), where NO and NO donors (NO mechanism) serve as a signaling molecule in the modulating tissue stress response for protect from oxygen glucose deprivations and from its elevations too.…”

Section: Nrf2 Functions Regulated By Nr4as Productive Pathway For Act...mentioning

confidence: 99%

GCs-beta and B-arrestins Regulate Nrf2 via NR4As Productive Pathway Mediated by B-adrenergic for Anti-inflammation and Adopting Myocardial and Immune Functions

Tantawi¹

2023

Jap J Clin & Med Res

1

0

View full text Add to dashboard Cite

The nuclear receptors “NR4As” productive pathway is the so important pathways for activating classic estrogen receptors and are important for regulating the adopted cellular anti-inflammatory growth (mediated by glucocorticoids, Nrf2, Ang2-AT2, and VEGF-A synthesis)which considered as the basic for B-arrestins synthesis which adopt B Adrenergic, and Nrf2 synthesis, that Nrf2 is strong activator to ACE functions for promoting Ang2-AT2 and VEGF-A synthesis for running the adopted anti-inflammatory growth and heme oxygenase. The modulation of oxidative stress will be done by serotonin synthesis (regulated by tryptophan “TGG”) which will promote melatonin synthesis which necessary to activate glucocorticoids productions via NR4A2 pathway followed by B-arrestins and Nrf2 productions for activating Ang2-AT2 and VEGF-A productions. That melatonin synthesis will be associated with GTPase production which promote and activate OPA1 repairs and functions, and responsible for activating glutamine synthesis which stabilize Leu functions through Nrf2 functions. This study concluded that NR4As productive pathway are the important pathway for improving anti-oxidation through improving IL6 productivity to IL17 productions, and is important for glucocorticoids-beta synthesis followed by B-arrestins productions which activate B Adrenergic synthesis that are necessary for activating Nrf2 production that followed by activating ACE for Ang2-AT2 and VEGF-A synthesis for running anti-inflammatory growth, modulating antioxidative stress, activate heme oxygenase, modulating brain function and memories growth , and activating T-cells and B-cell functions. That NR4As exert multilevel regulations of brain function and cardiac functions that protect immune survival from vascular cardiac diseases, and are the primary modulator to pro-inflammation and stimulator for variety of active genes and subunits started by estrogen and GCs-beta productions which followed by activating B-arrestins which activate B Adrenergic synthesis which has the roles of activating Nrf2 productions for adopting antioxidative functions, heme oxygenase, vasoconstriction functions, and anti-inflammatory growth mediated by Ang2-AT2 and VEGF-A synthesis.

show abstract

“…Glutamine(Gln) synergistically promotes mTORC1 activation with Leu via glutaminolysis and Leu absorption via an antiporter. However, Gln has also been shown to inhibit mTORC1 activity [58]. Also, L-leucine increases GDH activity and stimulates glutamate synthesis from different nitrogen sources by regulating mTORC1 [59].…”

Section: Nr4as Necessary For Activating Nrf2 Function Which Are Stron...mentioning

confidence: 99%

Glucocorticoid-Beta Regulate B-Adrenergic and Nrf2 via NR4As Productive Pathway For Activating Anti-Inflammation Include Antioxidant Functions and Myocardial Immune Functions

Tantawi¹

2023

Med Clin Sci

0

View full text Add to dashboard Cite

The nuclear receptors “NR4As” productive pathway is the so important pathways for activating classic estrogen receptors and are important for regulating the adopted cellular anti-inflammatory growth(mediated by glucocorticoids, Nrf2, Ang2-AT2, and VEGF-A synthesis) which considered as the basic for B-arrestins synthesis which adopt B Adrenergic, and Nrf2 synthesis, that Nrf2 is strong activator to ACE functions for promoting Ang2-AT2 and VEGF-A synthesis for running the adopted anti-inflammatory growth and heme oxygenase. The modulation of oxidative stress will be done by serotonin synthesis(regulated by tryptophan “TGG”) which will promote melatonin synthesis which necessary to activate glucocorticoids productions via NR4A2 pathway followed by B-arrestins and Nrf2 productions for activating Ang2-AT2 and VEGF-A productions. That melatonin synthesis will be associated with GTPase production which promote and activate OPA1 repairs and functions , and responsible for activating glutamine synthesis which stabilize Leucine functions through Nrf2 functions. This study concluded that NR4As productive pathway are the important pathway for improving antioxidation through improving IL6 productivity to IL17 productions, and is important for glucocorticoidsbeta synthesis followed by B-arrestins productions which activate B Adrenergic synthesis that are necessary for activating Nrf2 production that followed by activating ACE for Ang2-AT2 and VEGF-A synthesis for running anti-inflammatory growth, modulating antioxidative stress, activate heme oxygenase, modulating brain function and memories growth , and activating T-cells and B-cell functions. That NR4As exert multilevel regulations of brain function and cardiac functions that protect immune survival from vascular cardiac diseases, and are the primary modulator to pro-inflammation and stimulator for variety of active genes and subunits started by estrogen and GCs-beta productions which followed by activating B-arrestins which activate B Adrenergic synthesis which has the roles of activating Nrf2 productions for adopting antioxidative functions, heme oxygenase, vasoconstriction functions, and anti-inflammatory growth mediated by Ang2-AT2 and VEGF-A synthesis. NR4As pathway has the role of improving cytokines which produced by cDC2s for producing IL6 which improved to IL17 synthesis(upon synthase function and availability of glutamine for supporting Leu synthesis and functions) which necessary for modulating GCs-beta synthesis followed by both B-arrestins synthesis and B Adrenergic then followed by Nrf2 productions,(note ‘N-Acetyl Serotonin activate Nuclear Factor Erythroid 2-Related Factor 2 for Alleviating Oxidative Damage mediated through promoting glutamine synthesis for activating Leu necessary for Nrf2 functions) then followed by activating Ang2-AT2 and VEGF-A necessary for anti-inflammatory growth for T cell functions and B-cell functions(that MZ B-cells which characterized by NR4As expression possess a strong B-cell regulatory functions are the main activator to glucocorticoids, to B-arrestins, and to Nrf2 production for activating Ang2-AT2 and VEGF-A synthesis). Also, this study concluded that β3-adrenergic receptors has important roles for preventing myocardial fibrosis by modulating antioxidative function through activating Nrf2 synthesis that B-adrenergic regulated by B-arrestins via NR4As productive pathway for activating Nrf2 production, that NR4As is a very important pathway for modulating oxidative stress(starred by the stimulation and modulation by serotonin followed by melatonin) for protecting heart, brain and liver functions from oxidative damages and from irregular proliferation activities. Also the β3-adrenergic responsible for lipolysis , and has the role of adoptung both anti-inflammatory growth and antioxidstive processes through activating Nrf2 synthesis followed by activating Ang2-AT2 and VEGF-A productions via NR4As productive pathway(where NRF2’s has imp role is modulating stress response that can now be revised to be included the regulation of the basic functions of stem cells) , that NR4A2 pathway can be concluded to :-

show abstract

Co-ingestion of glutamine and leucine synergistically promotes mTORC1 activation

Cited by 4 publications

References 53 publications

Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes

Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes

GCs-beta and B-arrestins Regulate Nrf2 via NR4As Productive Pathway Mediated by B-adrenergic for Anti-inflammation and Adopting Myocardial and Immune Functions

Glucocorticoid-Beta Regulate B-Adrenergic and Nrf2 via NR4As Productive Pathway For Activating Anti-Inflammation Include Antioxidant Functions and Myocardial Immune Functions

Contact Info

Product

Resources

About