Sphingosine 1-Phosphate Metabolism and Signaling

Hu, Yan; Dai, Kezhi

doi:10.1007/978-981-19-0394-6_6

Cited by 8 publications

(2 citation statements)

References 97 publications

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“…Therefore, the deficiency of sphingosine in the MC group inhibits S1P production, resulting in impaired sphingolipid metabolism, ultimately leading to impaired pancreatic β cell function and insulin resistance. 82 In our study, when compared to the MC group, the levels of 3-ketosphinganine, sphinganine, and sphingosine significantly increased in the LIP and LIPA groups. These suggest that the improvement in insulin resistance and the restoration of pancreatic β cell morphology may be associated with the improvement of the sphingolipid metabolism.…”

Section: Discussionsupporting

confidence: 48%

The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice

Li,

Tong,

Shao

et al. 2024

Food Funct.

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Section: Discussionsupporting

confidence: 48%

The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice

Li,

Tong,

Shao

et al. 2024

Food Funct.

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“…Inflammation is a critical component of AKI, and sphingolipids are known to regulate cellular signaling pathways in inflammation (reviewed in). [7][8][9] Briefly, inflammatory cytokines, including TNFα and IL-6, activate sphingomyelinases that hydrolyze sphingomyelin to form ceramide which is then cleaved by ceramidases to yield sphingosine (Figure 1). Sphingosine kinases (SKs) phosphorylate the primary hydroxyl of sphingosine, forming sphingosine 1-phosphate (S1P) which promotes inflammation and cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice

Maines¹,

Green²,

Keller³

et al. 2022

IJNRD

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Acute kidney injury (AKI) is a common multifactorial adverse effect of surgery, circulatory obstruction, sepsis or drug/ toxin exposure that often results in morbidity and mortality. Sphingolipid metabolism is a critical regulator of cell survival and pathologic inflammation processes involved in AKI. Opaganib (also known as ABC294640) is a first-in-class experimental drug targeting sphingolipid metabolism that reduces the production and activity of inflammatory cytokines and, therefore, may be effective to prevent and treat AKI. Methods: Murine models of AKI were used to assess the in vivo efficacy of opaganib including ischemia-reperfusion (IR) injury induced by either transient bilateral occlusion of renal blood flow (a moderate model) or nephrectomy followed immediately by occlusion of the contralateral kidney (a severe model) and lipopolysaccharide (LPS)-induced sepsis. Biochemical and histologic assays were used to quantify the effects of oral opaganib treatment on renal damage in these models. Results: Opaganib suppressed the elevations of creatinine and blood urea nitrogen (BUN), as well as granulocyte infiltration into the kidneys, of mice that experienced moderate IR from transient bilateral ligation. Opaganib also markedly decreased these parameters and completely prevented mortality in the severe renal IR model. Additionally, opaganib blunted the elevations of BUN, creatinine and inflammatory cytokines following exposure to LPS. Conclusion:The data support the hypotheses that sphingolipid metabolism is a key mediator of renal inflammatory damage following IR injury and sepsis, and that this can be suppressed by opaganib. Because opaganib has already undergone clinical testing in other diseases , the present studies support conducting clinical trials with this drug with surgical or septic patients at risk for AKI.

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Therapies for lysosomal storage diseases: Principles, practice, and prospects for refinements based on evolving science

Grabowski

Mistry²

2022

Molecular Genetics and Metabolism

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Sphingosine 1-Phosphate Metabolism and Signaling

Cited by 8 publications

References 97 publications

The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice

The synergism of Lactobacillaceae, inulin, polyglucose, and aerobic exercise ameliorates hyperglycemia by modulating the gut microbiota community and the metabolic profiles in db/db mice

The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice

Therapies for lysosomal storage diseases: Principles, practice, and prospects for refinements based on evolving science

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