Poster abstracts
Poster number 102 submitted by Fnu Palwasha
Type 1 Diabetes therapeutic compound MSB-61: using RNA sequencing to identify the mechanism
Abstract:
Type 1 diabetes (T1D) is an autoimmune disease. Loss of beta cell mass and subsequent insulin insufficiency leads to hyperglycemia. Upon diagnosis with Type 1 Diabetes (T1D), insulin- secreting capacity has been reduced by an estimated 70-90%. Insulin remains the gold standard and the only effective treatment for T1D since its discovery 100 years ago. Protecting the beta cells from cytokine-induced cell death and restoring their ability to produce and secrete insulin are important to treat T1D.We have identified a dual-acting compound MSB-61, which addresses both issues. The aim of this study is to identify the mechanism of action of MSB-61 and to achieve this aim islets obtained from CD-1 mice were exposed for one hour to two minimal but viable dosages (10 and 50 uM) of MSB-61. After treatment, RNA was collected, and RNA sequencing was carried out. In addition to RNA extraction for sequencing, MSB-61's ability to secrete insulin was verified using an ELISA on control and 10 and 50 uM MSB-61-treated islets, and the activity of cell death was assessed using a cell death assay on control, MSB-61-treated, cytokine-treated, and cytokine + MSB-61 treated islets. We analyzed 57,010 genes (or non-coding transcripts) in our RNA seq data set and identified 67 differentially expressed genes (DEGs) based on >2-fold expression cut of analysis. According to the String database, the top 18 DEGs (>5-fold) are the most interactive genes and part of a common network in terms of biological pathways. If successful, a small molecule like MSB-61 could halt beta-cell destruction and stimulate enough endogenous insulin to restore normal blood glucose. As our lab is working for years on diabetes, the success of this project will open new ways in T1D prevention and treatment, identifying the genes and pathways targeted by MSB-61 can help us in improving our ways to approach diabetes and design and test more drugs.
Keywords: