S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes

He, Qiong; Bo, Jiaqi; Shen, Ruihua; Li, Yan; Zhang, Yi; Zhang, Jiaxin; Yang, Jing; Liu, Yunfeng

doi:10.1155/2021/1341750

Cited by 11 publications

(4 citation statements)

References 124 publications

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“… 41 S1P is a multifunctional bioactive lipid mediator, S1P can promote β cell proliferation and antagonize its apoptosis and insulin resistance in muscle tissue, playing a positive role in preventing and delaying the development of T2DM. 42 We are the first to report that davidiin can raise S1P. Therefore, we speculate that davidiin enhanced phospholipid metabolism promotes PI and S1P expression to play a hypoglycemic effect.…”

Section: Discussionmentioning

confidence: 76%

Unveiling the Pharmacological Mechanisms of Davidiin’s Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome

Li,

Zhou,

Huang

et al. 2024

DDDT

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Background Polygonum capitatum Buch.-Ham. ex D. Don ( P. capitatum ), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties. Materials and Methods Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS. Results Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins. Conclusion Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin’s action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.

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Section: Discussionmentioning

confidence: 76%

Unveiling the Pharmacological Mechanisms of Davidiin’s Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome

Li,

Zhou,

Huang

et al. 2024

DDDT

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“…Chronic inflammation, attributable to obesity, diabetes, diet, and pancreatitis, usually precedes pancreatic cancers [187,188]. Extensive studies have focused on SphK/S1P/S1PR and insulin signalling in pancreatic beta cells due to their importance in inflammation, insulin resistance, and diabetes [189,190]. More recently, SphK/S1P/S1PR signalling modulators are being investigated for hard-to-treat and chemo-resistant pancreatic cancers to overcome intrinsic and acquired drug resistance [191][192][193][194].…”

Section: S1p In Pancreatic Function and Cancermentioning

confidence: 99%

Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway

McGowan

Lin

Chen

2022

Cancers

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Incidence of gastrointestinal (GI) cancers is increasing, and late-stage diagnosis makes these cancers difficult to treat. Chronic and low-grade inflammation are recognized risks for most GI cancers. The GI mucosal immune system maintains healthy homeostasis and signalling molecules made from saturated fats, bioactive sphingolipids, play essential roles in healthy GI immunity. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, is a key mediator in a balanced GI immune response. Disruption in the S1P pathway underlies systemic chronic metabolic inflammatory disorders, including diabetes and GI cancers, providing a strong rationale for using modulators of the S1P pathway to treat pathological inflammation. Here, we discuss the effects of bioactive sphingolipids in immune homeostasis with a focus on S1P in chronic low-grade inflammation associated with increased risk of GI carcinogenesis. Contemporary information on S1P signalling involvement in cancers of the digestive system, from top to bottom, is reviewed. Further, we discuss the use of novel S1P receptor modulators currently in clinical trials and their potential as first-line drugs in the clinic for chronic inflammatory diseases. Recently, ozanimod (ZeposiaTM) and etrasimod have been approved for clinical use to treat ulcerative colitis and eosinophilic oesophagitis, respectively, which may have longer term benefits in reducing risk of GI cancers.

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“…S1P promotes proliferation and reduces the apoptosis of pancreatic beta-cells. Specifically, the upregulation of S1PR expression results in a hypoglycemic effect by increasing the number of beta-cells and insulin levels [ 93 ]. In addition, physiological concentrations of extracellular S1P inhibit the cytokine-induced apoptosis of beta-cells, again pointing towards a potentially protective function of S1P in T2D [ 94 ].…”

Section: S1p and Platelets In Diseasesmentioning

confidence: 99%

Platelet-Derived S1P and Its Relevance for the Communication with Immune Cells in Multiple Human Diseases

Tolksdorf

Moritz

Wolf

et al. 2022

IJMS

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Sphingosine-1-phosphate (S1P) is a versatile signaling lipid involved in the regulation of numerous cellular processes. S1P regulates cellular proliferation, migration, and apoptosis as well as the function of immune cells. S1P is generated from sphingosine (Sph), which derives from the ceramide metabolism. In particular, high concentrations of S1P are present in the blood. This originates mainly from erythrocytes, endothelial cells (ECs), and platelets. While erythrocytes function as a storage pool for circulating S1P, platelets can rapidly generate S1P de novo, store it in large quantities, and release it when the platelet is activated. Platelets can thus provide S1P in a short time when needed or in the case of an injury with subsequent platelet activation and thereby regulate local cellular responses. In addition, platelet-dependently generated and released S1P may also influence long-term immune cell functions in various disease processes, such as inflammation-driven vascular diseases. In this review, the metabolism and release of platelet S1P are presented, and the autocrine versus paracrine functions of platelet-derived S1P and its relevance in various disease processes are discussed. New pharmacological approaches that target the auto- or paracrine effects of S1P may be therapeutically helpful in the future for pathological processes involving S1P.

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S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes

Cited by 11 publications

References 124 publications

Unveiling the Pharmacological Mechanisms of Davidiin’s Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome

Unveiling the Pharmacological Mechanisms of Davidiin’s Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome

Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway

Platelet-Derived S1P and Its Relevance for the Communication with Immune Cells in Multiple Human Diseases

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