ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Contradictory Effects on Hepatocytes in ASMD.International journal of molecular sciences · 2026Review
- Reduced Sphingosine-1-Phosphate Levels Exacerbate Type 2 Diabetes Mellitus and Associated Complications in a High-Fat Diet Mouse Model.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Isoform-specific roles of AMP-activated protein kinase in cardiac physiology and pathophysiology.Frontiers in cardiovascular medicine · 2025Review
- Sphingosine-1-phosphate promotes liver fibrosis in metabolic dysfunction-associated steatohepatitis.PloS one · 2024Article
- Effect of FTY720P on lipid accumulation in HEPG2 cells.Scientific reports · 2023Article
- Functional roles of sphingolipids in immunity and their implication in disease.Experimental & molecular medicine · 2023Review
- Hepatocyte ABCA1 deficiency is associated with reduced HDL sphingolipids.Frontiers in physiology · 2023Article
- S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes.Journal of diabetes research · 2021Article
- Review
- Acid sphingomyelinase deficiency exacerbates LPS-induced experimental periodontitis.Oral diseases · 2020Article
- Role of Sphingosine Kinase in Type 2 Diabetes Mellitus.Frontiers in endocrinology · 2020Review
- Tricyclic antidepressant amitriptyline inhibits autophagic flux and prevents tube formation in vascular endothelial cells.Basic & clinical pharmacology & toxicology · 2019Article
- Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease.International journal of molecular sciences · 2018Review
- A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Sphingosine kinase and sphingosine-1-phosphate in liver pathobiology.Critical reviews in biochemistry and molecular biology · 2017Review
- Novel Interconnections in Lipid Metabolism Revealed by Overexpression of Sphingomyelin Synthase-1.The Journal of biological chemistry · 2017Article
- The role of sphingolipid signalling in diabetes‑associated pathologies (Review).International journal of molecular medicine · 2017Review
- Effective treatment with combination of peripheral 5-hydroxytryptamine synthetic inhibitor and 5-hydroxytryptamine 2 receptor antagonist on glucocorticoid-induced whole-body insulin resistance with hyperglycemia.Journal of diabetes investigation · 2016Article
- Acid Sphingomyelinase Promotes Endothelial Stress Response in Systemic Inflammation and Sepsis.Molecular medicine (Cambridge, Mass.) · 2016Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Acid sphingomyelinase (ASM) regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate (S1P). Because sphingolipids regulate AKT activation, we investigated the role of ASM in hepatic glucose and lipid metabolism. Initially, we overexpressed ASM in the livers of wild-type and diabetic db/db mice by adenovirus vector (Ad5ASM). In these mice, glucose tolerance was improved, and glycogen and lipid accumulation in the liver were increased. Using primary cultured hepatocytes, we confirmed that ASM increased glucose uptake, glycogen deposition, and lipid accumulation through activation of AKT and glycogen synthase kinase-3β. In addition, ASM induced up-regulation of glucose transporter 2 accompanied by suppression of AMP-activated protein kinase (AMPK) phosphorylation. Loss of sphingosine kinase-1 (SphK1) diminished ASM-mediated AKT phosphorylation, but exogenous S1P induced AKT activation in hepatocytes. In contrast, SphK1 deficiency did not affect AMPK activation. These results suggest that the SphK/S1P pathway is required for ASM-mediated AKT activation but not for AMPK inactivation. Finally, we found that treatment with high-dose glucose increased glycogen deposition and lipid accumulation in wild-type hepatocytes but not in ASM(-/-) cells. This result is consistent with glucose intolerance in ASM(-/-) mice. In conclusion, ASM modulates AKT activation and AMPK inactivation, thus regulating glucose and lipid metabolism in the liver.
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