The anti-diabetic potential of betaine. Mechanisms of action in rodent models of type 2 diabetes

Szkudelska, Katarzyna; Szkudelski, Tomasz

doi:10.1016/j.biopha.2022.112946

Cited by 19 publications

(11 citation statements)

References 81 publications

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“…Interestingly, we found that betaine and methionine are reduced in the kidney, liver, and heart of young diabetic animals prior to development of end-organ complications. These findings are consistent with previous reports showing that the tissue content of betaine is reduced in type 2 diabetes ( 39 ). Furthermore, it has been recently reported that, in the SURDIAGENE (SURvival DIAbetes and GENEtics) study with a large, prospective cohort of patients with type 2 diabetes, betaine and homocysteine were associated with hospitalization for heart failure and/or mortality and that homocysteine was an independent predictor of all-cause mortality ( 30 ).…”

Section: Discussionsupporting

confidence: 94%

Section: Sglt2i Effects On One Carbon Metabolism and The Methionine C...supporting

confidence: 94%

“…Furthermore, it has been recently reported that, in the SURDIAGENE (SURvival DIAbetes and GENEtics) study with a large, prospective cohort of patients with type 2 diabetes, betaine and homocysteine were associated with hospitalization for heart failure and/or mortality and that homocysteine was an independent predictor of all-cause mortality ( 30 ). Rodent studies show that betaine supplementation ameliorated oxidative and ER stress and reduced inflammation, in part, through activation of AMPK ( 39 ). Of note, we found that treatment with SGLT2i as well as insulin increased hepatic betaine and decreased homocysteine levels.…”

Section: Discussionmentioning

confidence: 99%

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Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition

Kogot-Levin¹,

Riahi²,

Abramovich³

et al. 2023

JCI Insight

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Diabetes is associated with increased risk for kidney and liver diseases, congestive heart failure, and mortality. Urinary glucose excretion using sodiumglucose cotransporter 2 (SGLT2) inhibitors prevents these adverse outcomes, however the mechanisms involved are not clear. Herein, we generated a roadmap of the metabolic alterations that occur in the kidney, liver, and heart in diabetes and in response to SGLT2 inhibition. We performed in vivo metabolic labeling with 13 C-glucose in normoglycemic and diabetic mice treated with or without the SGLT2 inhibitor dapagliflozin, followed by simultaneous metabolomics and metabolic flux analyses in different organs and the plasma.We found that in diabetes, glycolysis and glucose oxidation are impaired in the kidney, liver, and heart. Treatment with dapagliflozin failed to rescue glycolysis and further inhibited pyruvate kinase activity in the liver. SGLT2 inhibition increased glucose oxidation in all organs; in the kidney, this effect was associated with modulation of the redox state, which may protect against oxidative stress. In addition, diabetes was associated with altered methionine cycle metabolism, evident by decreased betaine and methionine levels, whereas treatment with SGLT2i increased hepatic betaine along with decreased homocysteine levels. mTORC1 activity was inhibited by SGLT2i along with stimulation of AMPK in both normoglycemic and diabetic animals, possibly explaining the protective effects against kidney, liver, and heart diseases. Collectively, our findings suggest that SGLT2i induces metabolic reprogramming orchestrated by AMPK-mTORC1 signaling with common and distinct effects in various tissues with implications for diabetes and aging.

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Section: Discussionsupporting

confidence: 94%

Section: Sglt2i Effects On One Carbon Metabolism and The Methionine C...supporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition

Kogot-Levin¹,

Riahi²,

Abramovich³

et al. 2023

JCI Insight

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“…Therefore, it is safe to consume vegetables that contain trigonelline, such as Gonostegia hirta , in moderation [ 61 ]. Some studies have shown that betaine has anti-inflammatory and antioxidant properties, and is also beneficial to alleviates endoplasmic reticulum stress, and therefore contributes to improve insulin sensitivity and better glucose clearance, with a greater potential to fight diabetes [ 62 ]. Caffeine is naturally found in various foods, such as coffee, tea, and cocoa, and has also been detected in Gonostegia hirta .…”

Section: Resultsmentioning

confidence: 99%

Nutritional Composition and Antioxidant Activity of Gonostegia hirta: An Underexploited, Potentially Edible, Wild Plant

Chen

Bao-cheng

et al. 2023

Plants

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Wild, edible plants have received increasing attention as an important complement to cultivate vegetables, as they represent an easily accessible source of nutrients, mineral elements, and antioxidants. In this study, the tender stems and leaves of Gonostegia hirta, an edible species for which only scarce data are available in the literature, are thoroughly evaluated for their nutritional profile, chemical characterization, and antioxidant activity. Being considered as an underexploited, potentially edible plant, the nutritional composition of Gonostegia hirta was identified, and several beneficial compounds were highlighted: sugars, potassium, calcium, organic acids, fatty acids, phenolics, and flavonoids. A total of 418 compounds were identified by metabolomic analysis, including phenolic acids, flavonoids, amino acids, lipids, organic acids, terpenoids, alkaloids, nucleotides, tannins, lignans, and coumarin. The plant sample was found to have good antioxidant capacities, presented by DPPH, FRAP, ABTS+, hydroxyl radical scavenging capacity, and its resistance to the superoxide anion radical test. In general, Gonostegia hirta has a good nutritional and phytochemical composition. The health benefits of Gonostegia hirta as a vegetable and herbal medicine is important for both a modern diet and use in medication.

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“…Betaine, the main bioactive compound of LF, is an amino-acid derivative, which can increase glycogen synthesis [ 25 ] and myoblast differentiation and PGC-1α-mediated mitochondrial biogenesis [ 26 ]. Increasing evidence indicates that betaine is associated with therapeutic potential in insulin-sensitive tissues, such as skeletal muscle, adipose tissue, and liver [ 27 ]. However, the mechanism of action of GEJ on skeletal muscle remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Guilu Erxian Jiao enhances protein synthesis, glucose homeostasis, mitochondrial biogenesis and slow-twitch fibers in the skeletal muscle

Fang¹,

Chang²,

Tsai³

et al. 2023

Journal of Food and Drug Analysis

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Guilu Erxian Jiao (GEJ) is a commonly used nutritional supplement due to its rich content of amino acids. It is also a traditional herbal medicine for improving degenerative joint. This study aimed to investigate the effect and mechanism of GEJ water extract (GEJ-WE) on skeletal muscle in C2C12 myotubes and C57BL/6J mice. Analysis of GEJ-WE were performed by high-performance liquid chromatography fingerprinting with chemical standards. Protein expression, mRNA level, glycogen content, mitochondria activity and ATP level were evaluated by western blots, real-time PCR, PAS staining, MTT and ATP bioluminescence assay, respectively. Skeletal muscle strength was evaluated by grip strength. Skeletal muscle volume, mass and fiber types were evaluated by micro computed tomography, histological analysis and immunofluorescence staining, respectively. Motor function was evaluated by rotarod performance and locomotor activity. In C2C12 myotubes, GEJ-WE significantly enhanced myogenic differentiation and myotube growth, protein synthesis signaling IGF-1/IGF-1R/IRS-1/Akt, Glut4 translocation, glycogen content, mitochondrial biogenesis signaling PGC-1α/NRF1/TFAM, mitochondrial activity and ATP production. However, IGF-1R antagonist AG1024 and PI3K inhibitor wortmannin reduced GEJ-WE-induced protein expression of MyHC, p-Akt, p-mTOR and p-GSK-3β, Glut4 translocation and glycogen content. In C57BL/6J mice, GEJ-WE not only upregulated protein synthesis and mitochondrial biogenesis signaling, but it also increased muscle volume, relative muscle weight, cross-sectional area of myofibers, glycogen content and transition of fast-to-slow type fibers of skeletal muscles. Moreover, GEJ-WE enhanced grip strength and motor activity of mice. In conclusion, the upregulation of protein synthesis, myogenic differentiation, glucose homeostasis, mitochondrial biogenesis and slow-twitch fibers contributes to the mechanisms of GEJ-WE on the enhancement of skeletal muscle mass and motor function.

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The anti-diabetic potential of betaine. Mechanisms of action in rodent models of type 2 diabetes

Cited by 19 publications

References 81 publications

Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition

Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition

Nutritional Composition and Antioxidant Activity of Gonostegia hirta: An Underexploited, Potentially Edible, Wild Plant

Guilu Erxian Jiao enhances protein synthesis, glucose homeostasis, mitochondrial biogenesis and slow-twitch fibers in the skeletal muscle

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