ArticleAmerican journal of physiology. Renal physiology2015
Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Lipid homeostasis in diabetic kidney disease.International journal of biological sciences · 2024Pooled it
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Altered glycolipid metabolism during acute kidney injury exacerbates renal inflammation.Scientific reports · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Renal Lipid Alterations From Diabetes to Early-Stage Diabetic Kidney Disease and Mitophagy: Focus on Cardiolipin.Journal of cellular and molecular medicine · 2025Article
- Nanopore-based full-length transcriptome sequencing for understanding the underlying molecular mechanisms of rapid and slow progression of diabetes nephropathy.BMC medical genomics · 2024Article
- Enzymes of sphingolipid metabolism as transducers of metabolic inputs.Biochemical Society transactions · 2024Review
- Sphingolipids and Chronic Kidney Disease.Journal of clinical medicine · 2024Review
- Urinary sphingolipids in adolescents and young adults with youth-onset diabetes.Pediatric nephrology (Berlin, Germany) · 2024Article
- Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy.Genes & genomics · 2024Article
- Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes.Biomedicines · 2024Article
- Bioinformatics to Identify Biomarkers of Diabetic Nephropathy based on Sphingolipid Metabolism and their Molecular Mechanisms.Current diabetes reviews · 2024Article
- Immunolocalization of Sphingolipid Catabolism Enzymes along the Nephron: Novel Early Urinary Biomarkers of Renal Damage.International journal of molecular sciences · 2023Article
- Metabolic Markers and Association of Biological Sex in Lupus Nephritis.International journal of molecular sciences · 2023Article
- Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae.Cells · 2023Article
- Lipidomics Profiling Reveals Serum Phospholipids Associated with Albuminuria in Early Type 2 Diabetic Kidney Disease.ACS omega · 2023Article
- Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications.International journal of molecular sciences · 2023Review
- Analysis of circulating ceramides and hexosylceramides in patients with coronary artery disease and type II diabetes mellitus.BMC cardiovascular disorders · 2023Article
- Unraveling the Crosstalk between Lipids and NADPH Oxidases in Diabetic Kidney Disease.Pharmaceutics · 2023Review
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Glycosphingolipids (GSLs) play a role in insulin resistance and diabetes, but their role in diabetic nephropathy (DN) has received limited attention. We used 9- and 17-wk-old nondiabetic db/m and diabetic db/db mice to examine the role of GSLs in DN. Cerebrosides or monoglycosylated GSLs [hexosylceramides (HexCers); glucosyl- and galactosylceramides] and lactosylceramide (LacCers) were elevated in db/db mouse kidney cortices, specifically in glomeruli, and also in urine. In our recent paper (25), we observed that the kidneys exhibited glomerular hypertrophy and proximal tubular vacuolization and increased fibrosis markers at these time points. Mesangial cells contribute to hyperglycemia-induced glomerular hypertrophy in DN. Hyperglycemic culture conditions, similar to that present in diabetes, were sufficient to elevate mesangial cell HexCers and increase markers of fibrosis, extracellular matrix proteins, and cellular hypertrophy. Inhibition of glucosylceramide synthase or lowering glucose levels decreased markers of fibrosis and extracellular matrix proteins and reversed mesangial cell hypertrophy. Hyperglycemia increased phosphorylated (p)SMAD3 and pAkt levels and reduced phosphatase and tensin homolog levels, which were reversed with glucosylceramide synthase inhibition. These data suggest that inhibition of glucosylceramide synthase reversed mesangial cell hypertrophy through decreased pAkt and pSmad3 and increased pathways responsible for protein degradation. Importantly, urinary GSL levels were higher in patients with DN compared with healthy control subjects, implicating a role for these lipids in human DN. Thus, hyperglycemia in type II diabetes leads to renal dysfunction at least in part by inducing accumulation of HexCers and LacCers in mesangial cells, resulting in fibrosis, extracellular matrix production, and hypertrophy.
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