Diabetes mellitus (DM) is a systemic metabolic disease that affects 463 million adults worldwide and is a leading cause of cardiovascular disease, blindness, nephropathy, peripheral neuropathy, and lower-limb amputation. Lipids have long been recognized as contributors to the pathogenesis and pathophysiology of DM and its complications, but recent discoveries have highlighted ceramides, a class of bioactive sphingolipids with cell signaling and second messenger capabilities, as particularly important contributors to insulin resistance and the underlying mechanisms of DM complications. Besides their association with insulin resistance and pathophysiology of type 2 diabetes, evidence is emerging that certain species of ceramides are mediators of cellular mechanisms involved in the initiation and progression of microvascular and macrovascular complications of DM. Advances in our understanding of these associations provide unique opportunities for exploring ceramide species as potential novel therapeutic targets and biomarkers. This review discusses the links between ceramides and the pathogenesis of DM and diabetic complications and identifies opportunities for novel discoveries and applications.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107734 | DOI Listing |
Dermatitis
January 2025
Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
The pathogenesis of atopic dermatitis (AD) points to skin barrier dysfunction as a critical piece of the puzzle. Deficiencies in fatty acids and ceramides-key elements of the skin barrier-have been linked to AD. Fatty acids can be separated into omega-3 and omega-6, which can be found in a variety of foods such as fish, nuts, seeds, and even plants.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Retinal degenerative diseases lead to irreversible vision loss due to photoreceptor cell death, driven by complex genetic and environmental factors. Ceramide, a sphingolipid metabolite, emerges as a critical mediator in the apoptotic cascade associated with retinal degeneration. Our previous work demonstrated L-Cycloserine's ability to protect photoreceptor-derived cells from oxidative stress by inhibiting the de novo ceramide pathway and thus prompting further investigation on its effect in the in vivo retina.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
The human voltage-gated proton channel (H1) provides an efficient proton extrusion pathway from the cytoplasm contributing to the intracellular pH regulation and the oxidative burst. Although its pharmacological inhibition was previously shown to induce cell death in various cell types, no such effects have been examined in polarized macrophages albeit H1 was suggested to play important roles in these cells. This study highlights that 5-chloro-2-guanidinobenzimidazole (ClGBI), the most widely applied H1 inhibitor, reduces the viability of human THP-1-derived polarized macrophages at biologically relevant doses with M1 macrophages being the most, and M2 cells the least sensitive to this compound.
View Article and Find Full Text PDFJ Orthop Surg Res
December 2024
Graduate School, Bengbu Medical University, Bengbu, 233030, Anhui, China.
Objective: To explore the effects of subanesthetic dose of esketamine on serum inflammatory factor levels and depressive mood in elderly patients with sarcopenia postoperatively.
Methods: This study retrospectively included 102 elderly patients who underwent elective total knee arthroplasty from April 2023 to June 2024 with skeletal muscle mass index (SMI) meeting the diagnostic criteria for sarcopenia (male SMI < 42.6 cm/m, female SMI < 30.
Front Cell Dev Biol
December 2024
Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Zagreb, Croatia.
Gliomas are highly aggressive primary brain tumors, with glioblastoma multiforme being the most severe and the most common one. Aberrations in sphingolipid metabolism are a hallmark of glioma cells. The sphingolipid rheostat represents the balance between the pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), and in gliomas it is shifted toward cell survival and proliferation, promoting gliomas' aggressiveness, cellular migration, metastasis, and invasiveness.
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