SMPDL3b modulates insulin receptor signaling in diabetic kidney disease

• Published in: Nature communications Vol. 10; no. 1; pp. 2692 - 16
• Main Authors: Mitrofanova, A., Mallela, S. K., Ducasa, G. M., Yoo, T. H., Rosenfeld-Gur, E., Zelnik, I. D., Molina, J., Varona Santos, J., Ge, M., Sloan, A., Kim, J. J., Pedigo, C., Bryn, J., Volosenco, I., Faul, C., Zeidan, Y. H., Garcia Hernandez, C., Mendez, A. J., Leibiger, I., Burke, G. W., Futerman, A. H., Barisoni, L., Ishimoto, Y., Inagi, R., Merscher, S., Fornoni, A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.06.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 13/31; 13/51; 14/19; 14/28; 147/143; 38/44; 38/77; 38/88; 38/90; 42/40; 45/22; 45/41; 631/443/272/1684/1587/2101; 631/80/86/2367; 64/60; 692/699/1585/2759/1419; 82/58; 82/80; 96/34; Animals; Antigens, CD - metabolism; Caveolin; Caveolin 1 - metabolism; Caveolin-1; Cell Line; Cell Membrane - metabolism; Ceramide; Ceramides - metabolism; Ceramides - therapeutic use; Complications; Cyclic Nucleotide Phosphodiesterases, Type 3 - genetics; Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism; Diabetes; Diabetes mellitus; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - pathology; Diabetic nephropathy; Disease Models, Animal; Female; Fluidity; Glucose; Humanities and Social Sciences; Humans; Insulin; Insulin - metabolism; Isoforms; Kidney diseases; Kidneys; Lipids; Male; Medicin och hälsovetenskap; Mice; Mice, Knockout; multidisciplinary; Phosphodiesterase; Podocytes - cytology; Podocytes - metabolism; Protein Isoforms - metabolism; Receptor, Insulin - metabolism; Renal cortex; Science; Science (multidisciplinary); Signal Transduction; Signaling; Sphingolipids; Sphingomyelin phosphodiesterase; Sphingomyelin Phosphodiesterase - metabolism; Supplements; Treatment Outcome

Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by in...