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Novel Signalling Cascade Blockade May Be the Answer to Type 1 Diabetes Prevention

PREVENTION of Type 1 diabetes mellitus (T1DM) development in patients may now be a possibility, according to a paper published by Dr Carolin Daniel and team at the Institute of Diabetes Research (IDF), Helmholtz Zentrum München, Neuherberg, Germany.

As an autoimmune disease characterised as aberrant islet autoantibody attack of beta cells within the pancreas, T1DM currently has no cure and therefore patients are required to monitor and maintain their own blood glucose levels on a daily basis; both hyper and hypoglycaemia can prove fatal. Insulin-specific T follicular helper (Tfh) cells are responsible for the support of high affinity B cell antibody production, which is a fundamental mechanism already established in T1DM pathogenesis.

Dr Daniel and colleagues analysed the biobank blood samples children, a scheme originally implemented by Prof Anette-Gabriele Ziegler, director of the IDF. An increased population of CXCR5+CD4Tfh precursors was seen to correlate with high miRNA92a expression in early autoimmune attack of pancreatic beta cells. This precursor induction was found to depend on signalling through the complex phosphatase and tensin homolog/phosphoinositol-3 kinase (PTEN/PI3K) network, directly acting through Krupple-like factor 2 (KLF2). To develop this further using non-obese diabetic (NOD) mice, researchers were able to utilise a miRNA92a antagomir to significantly reduce dysregulated pancreatic immune cell infiltration and decrease the population of Tfh precursors evident in both the periphery and lymph nodes. Comparatively, the infiltration of regulatory T cells was seen to increase with treatment.

The targeting of microRNAs has long been discussed within clinical research, but this study represents great potential for the treatment of diabetes. Commenting on this advancement in immunological-based therapy, Prof Ziegler elucidated: “The targeted inhibition of miRNA92a or the downstream signalling pathway could open up new possibilities for the prevention of Type 1 diabetes.” In addition to drug development, this revelation of Tfh correlation with disease progression may also prove significant within the ever-growing field of disease biomarkers.

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