Lowering Plasma 1-Deoxysphingolipids Improves Neuropathy in Diabetic Rats

• DOI: 10.2337/db14-1325
• Publication Date: 2014-10-03T01:21:19Z
• Authors: Alaa Othman; Roberto Bianchi; Irina Alecu; Yu Wei; Carla Porretta-Se...; Raffaella Lombardi; Alessia Chiorazzi; Cristina Meregalli; Norberto Oggioni; Guido Cavaletti; Giuseppe Lauria; Arnold von Eckard...; Thorsten Hornemann
• Keywords: Diabetic Neuropathy; Therapeutic effect

1-Deoxysphingolipids (1-deoxySLs) are atypical neurotoxic sphingolipids that formed by the serine-palmitoyltransferase (SPT). Pathologically elevated 1-deoxySL concentrations cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), an axonal associated with several missense mutations in SPT. Oral L-serine supplementation suppressed formation of 1-deoxySLs patients HSAN1 preserved nerve function mouse model. Because also 2 diabetes mellitus, could be a therapeutic option for diabetic (DN). This was tested STZ rats preventive treatment scheme. Diabetic showed significantly increased plasma concentrations, lowered both schemes (P < 0.0001). had no significant effect on hyperglycemia, body weight, or food intake. Mechanical sensitivity improved 0.01) 0.001). Nerve conduction velocity (NCV) only group 0.05). Overall NCV highly = 5.2E-12) inverse correlation concentrations. In summary, our data support hypothesis involved pathology DN oral novel treating DN.