Proteomic quantitative study of dorsal root ganglia and sciatic nerve in type 2 diabetic mice

Diabetes; Dorsal root ganglia; Sciatic nerveDiabetes; Ganglios de la raíz dorsal; Nervio ciáticoDiabetis; Ganglis de l'arrel dorsal; Nervi ciàticObjective Peripheral neuropathy is the most common and debilitating complication of type 2 diabetes, leading to sensory loss, dysautonomia, hyperalgesia, and spontaneous noxious sensations. Despite the clinical and economic burden of diabetic neuropathy, no effective treatment is available. More preclinical research must be conducted in order to gain further understanding of the aetiology of the disease and elucidate new therapeutic targets. Methods The proteome of lumbar dorsal root ganglia and sciatic nerve of BKS-db/db mice, which contain a mutation of the leptin receptor and are an established type 2 diabetes model, was characterized for the first time by tandem mass tag labelling and mass spectrometry analysis. Results Proteomic analysis showed differentially expressed proteins grouped into functional clusters in db/db peripheral nerves compared to control mice, underlining reduced glycolytic and TCA cycle metabolism, higher lipid catabolism, upregulation of muscle-like proteins in DRG and downregulation in SCN, increased cytoskeleton-related proteins, a mild dysregulation of folding chaperones, activation of acute-phase and inflammatory response, and alterations in glutathione metabolism and oxidative stress related proteins. Conclusions Our data validate previous transcriptomic and metabolomic results and uncover new pathways altered in diabetic neuropathy. Our results point out that energetic deficiency could represent the main mechanism of neurodegeneration observed in diabetic neuropathy. These findings may provide important information to select appropriate targets to develop new therapeutic strategies.This work was supported by the Fundació Marató TV3 (grant 201607.10) and 2017 SGR1468 to M.C. M.L.J, A.O and S.V are recipients of predoctoral fellowships from Generalitat de Catalunya (2019FI_B2 00061; 2020FI_B2 00037 and 2020FI_B1 00054, respectively). The authors declare that there is no conflict of interest