β-alanine scavenging of free radicals protects mitochondrial function and enhances both insulin secretion and glucose uptake in cells under metabolic stress

Billacura, Merell P.; Lavilla, Charlie; Cripps, Michael J.; Hanna, Katie; Sale, Craig; Turner, Mark D.

doi:10.1016/j.arres.2022.100050

Cited by 12 publications

(6 citation statements)

References 28 publications

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“…The eventual escalation in the number of confirmed diabetes patients in the contemporary world is one of the critical health issues facing health authorities, with the number of patients expected to increase to 366 million by 2030, thus becoming the seventh leading cause of death [1][2][3]. Diabetes is a known type of clinical pancreatic syndrome and is categorized into two common types: (1) type-1 (T1-DM) and (2) type-2 (T2-DM).…”

Section: Introductionmentioning

confidence: 99%

Insight into the Potential Antioxidant and Antidiabetic Activities of Scrolled Kaolinite Single Sheet (KNs) and Its Composite with ZnO Nanoparticles: Synergetic Studies

et al. 2023

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The kaolinite sheets were scrolled by sonication-induced chemical delamination processes into well-developed nanotubes (KNs) which were used as substrates for microwave-based ZnO nanoparticles (ZnO/KNs). The biological activities of synthetic ZnO/KNs structures, in terms of the antioxidant and antidiabetic properties, were assessed in comparative studies with the separated phases of the synthetic ZnO and KNs as well as the commercially used ZnO. The KNs substrate resulted in a notable enhancement in the antioxidant and antidiabetic properties of ZnO, which was assigned positive influence on the surface area, interactive interfaces, charge separation, and agglomeration properties of ZnO in addition to the detectable bioactive properties of the KNs structure. The ZnO/KNs structure achieved remarkable scavenging efficiencies for 1, 1-diphenyl-2-picrylhydrazil (DPPH) (89.8 ± 1.57%), nitric oxide (90.6 ± 1.63%), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) (86.8 ± 1.28%), and superoxide (43.9 ± 1.72%) radicals. Additionally, it shows high inhibition effects on porcine α-amylase (84.3 ± 1.92%), crude α-amylase (70.6 ± 1.37%), pancreatic α-Glucosidase (94.7 ± 1.54%), crude α-Glucosidase (95.4 ± 1.64%), and amyloglucosidase (95.3 ± 1.32%) enzymes. This antidiabetic activity is significantly higher than the activity of miglitol and close to or slightly higher than acarbose, which leads us to recommend the use of ZnO/KNs when considering the cost and side effects of the commercially used drugs.

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Section: Introductionmentioning

confidence: 99%

Insight into the Potential Antioxidant and Antidiabetic Activities of Scrolled Kaolinite Single Sheet (KNs) and Its Composite with ZnO Nanoparticles: Synergetic Studies

et al. 2023

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“…Beta-alanine plays an essential role in the synthesis of carnosine, a dipeptide found primarily in muscle tissue [ 42 ]. Carnosine contributes to various physiological processes in the body, including buffering acidity in muscle cells, reducing oxidative stress, and regulating glucose metabolism [ 43 ]. Additionally, carnosine has been found to inhibit the proliferation of breast, ovarian, colon, and leukemic cancer cells [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…The elevated beta-alanine levels induced by PEDF may have broader implications in the context of cancer biology and metabolic disorders. Beta-alanine, as a component of carnosine, can modulate intracellular pH and act as an antioxidant [ 43 ], potentially influencing cancer cell proliferation, survival, and response to oxidative stress [ 42 ]. Moreover, dysregulation of beta-alanine metabolism has been linked to metabolic disorders, suggesting that the PEDF-mediated increase in beta-alanine levels may have implications for metabolic homeostasis.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Pigment-Epithelium-Derived Factor on MCF-7 Cell Metabolism in the Context of Glycaemic Condition

et al. 2023

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Studies have demonstrated that pigment-epithelium-derived factor (PEDF) is a robust inhibitor of tumour growth and development, implying that this may serve as a promising target for therapeutic intervention. However, the precise impact of PEDF on cancerous cell metabolic pathways remains uncertain despite ongoing research. In this light, this study aimed to employ a metabolomics approach for understanding the metabolic reprogramming events in breast cancer across different glycaemic loads and their response to PEDF. Gas chromatography-quadrupole mass spectrometry (GC/Q-MS) analysis revealed metabolic alterations in ER+ human cell line MCF-7 cells treated with PEDF under varying glycaemic conditions. The identification of significantly altered metabolites was accomplished through MetaboAnalyst (v.5.0) and R packages, which enabled both multivariate and univariate analyses. Out of the 48 metabolites identified, 14 were chosen based on their significant alterations in MCF-7 cells under different glycaemic conditions and PEDF treatment (p < 0.05, VIP > 0.8). Dysregulation in pathways associated with amino acid metabolism, intermediates of the TCA cycle, nucleotide metabolism, and lipid metabolism were detected, and they exhibited different responses to PEDF. Our results suggest that PEDF has a diverse influence on the metabolism of MCF-7 cells in both normo- and hyperglycaemic environments, thereby warranting studies using patient samples to correlate our findings with clinical response in the future.

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“…Of note, there was a remarkable increase in glutathione only in the refed group. Glucose levels in the refed animals did not reach the same levels as in the fed regimen, which could be a result of increased glucose uptake in cells induced by ß-alanine (Billacura et al, 2022). Pathway analysis to assess this process in more depth confirmed that pathways for ‘glycolysis’, ‘Warburg effect’ and ‘pyruvate metabolism’ were all significantly dampened during fasting, whilst there was a significant enrichment for ‘fatty acid metabolism’, ‘bile acid homeostasis’ and ‘taurine/hypotaurine metabolism’ (Figure 5G).…”

Section: Main Textmentioning

confidence: 99%

Beneficial effects of intermittent fasting in NASH and subsequent HCC development are executed by concerted PPARα and PCK1 action in hepatocytes

Gallage,

Ali,

Barragan Avila

et al. 2023

Preprint

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The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen (two non-consecutive days of food deprivation per week), initiated in the active phase of mice, prevents/ameliorates NASH and fibrosis as well as reduces subsequent HCC development without affecting total calorie intake. The timing, length and number of fasting cycles as well as the type of NASH diet were all critical parameters determining the effectiveness of the fasting benefits. Combined proteomic, transcriptomic and metabolomic analyses identified that PPAR alpha and glucocorticoid receptor (GR)-PCK1 act co-operatively as hepatic executors of the fasting response by promoting fatty acid catabolism and gluconeogenesis whilst suppressing anabolic lipogenesis. In line, PPAR alpha targets and PCK1 were reduced in human NASH. Additionally, dynamic [18F]FDG-PET analysis in vivo revealed increased [18F]FDG uptake/retention and enhanced gluconeogenesis in the liver upon fasting (in accordance with PPAR alpha and GR-PCK1 activation) when assessed by compartmental modelling. Hepatocyte-specific GR deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivo abolished the beneficial outcomes of fasting against inflammation and fibrosis, confirming their causal relationship in integrating systemic signalling in hepatocytes. Notably, PPAR alpha agonist pemafibrate recapitulated key aspects of hepatic fasting signalling at a molecular level. Therefore, IF or pharmacological mimetics of the PPAR alpha and/or GR-PCK1 axis could be a viable intervention against NASH and subsequent liver cancer.

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β-alanine scavenging of free radicals protects mitochondrial function and enhances both insulin secretion and glucose uptake in cells under metabolic stress

Cited by 12 publications

References 28 publications

Insight into the Potential Antioxidant and Antidiabetic Activities of Scrolled Kaolinite Single Sheet (KNs) and Its Composite with ZnO Nanoparticles: Synergetic Studies

Insight into the Potential Antioxidant and Antidiabetic Activities of Scrolled Kaolinite Single Sheet (KNs) and Its Composite with ZnO Nanoparticles: Synergetic Studies

The Impact of Pigment-Epithelium-Derived Factor on MCF-7 Cell Metabolism in the Context of Glycaemic Condition

Beneficial effects of intermittent fasting in NASH and subsequent HCC development are executed by concerted PPARα and PCK1 action in hepatocytes

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