Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes

Abstract

Aims Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes. The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior interosseous nerve (PIN) have proposed PIN a useful indicator of DPN. Methods A quantitative mass spectrometry‐based proteomics analysis was made of peripheral nerves from age‐ and gender‐matched living human male tissue donors; nine type 2 diabetes subjects, with decreased sural nerve action potentials indicating DPN, and six controls without type 2 diabetes, with normal electrophysiology results. Results A total of 2617 proteins were identified. Linear regression was used to discover which proteins were differentially expressed between type 2 diabetes and controls. Only soft signals were found. Therefore, clustering of the 500 most variable proteins was made to find clusters of similar proteins in type 2 diabetes subjects and healthy controls. Conclusions This feasibility study shows, for the first time, that the use of quantitative mass spectrometry enables quantification of proteins from nerve biopsies from subjects with and without type 2 diabetes, which may aid in finding biomarkers of importance to DPN development.

Carpal Tunnel Syndrome and Diabetes—A Comprehensive Review

“…Interestingly, details of normal as well as degenerating and regenerating nerve fibres have been visualised, particularly the architecture of regenerative clusters in nerve biopsies from diabetic subjects [ 110 ] ( Figure 3 ). This novel technique can be combined with mass spectrometry to analyse the proteomics in the nerve biopsies [ 111 ]. Identification of individuals at risk for the development of neuropathy, as well as CTS or UNE at the elbow, is crucial, with the intention of appropriately timed diagnosis and treatment [ 9 ].…”

Quantification of heat shock proteins in the posterior interosseous nerve among subjects with type 1 and type 2 diabetes compared to healthy controls

“…Diabetes is a global pandemic, with an estimated prevalence of approximately 537 million affected people, diagnosed either as type 1 diabetes (T1D) or type 2 diabetes (T2D) (IDF, 2021). Numbers are expected to rise over the years to come.…”

“…Several challenges arise from studying the full proteome of a cell or tissue, such as high volumes of data, the complex nature of proteomes, and the dynamic nature of the proteome (Manzoni et al, 2018 ). We have previously described the full proteome of PIN in subjects with T2D, demonstrating early signs of DPN, and in healthy controls, using quantitative mass spectrometry (Ising et al, 2021 ).…”

Carpal Tunnel Syndrome and Ulnar Nerve Entrapment at the Elbow Are Not Associated With Plasma Levels of Caspase-3, Caspase-8 or HSP27

“…Small heat shock proteins (sHSP) protect cells from outer stress, such as toxic chemicals, oxidative stress and heat shock (Acunzo et al, 2012), and are detected in human nerve biopsies both from healthy and diabetic subjects (Ising et al, 2021). In particular, HSP27 plays a major role in inhibiting apoptosis (Hunt et al, 2012) and reduces ischemic damage following a stroke (Sharp et al, 2013;Teramoto et al, 2013).…”