Rasoul Salehi, Ahmad Raza Salehi, Nasimeh Vatandoust and Sedigheh Momenzadeh
Isfahan University of Medical Sciences, Iran
Posters & Accepted Abstracts: J Diabetes Metab
It has now become obvious that the pathophysiological defects leading to type 2 diabetes (T2D) is much more complex than thought before. Insulin resistance is an early event in the course of T2D development. The transition from normoglycemy to pre-diabetes is usually a gradual phenomenon that occurs over 5-10 years during which the disease remains undetected. Among the routinely practiced T2D screening criteria, like, FPG, IFG, IGT or HbA1c, still the issue of a preferable one is debated. Here I present more precise noninvasive pre-symptomatic diagnosis and risk assessment strategies including non-coding RNAs signature in peripheral blood. Life style changes with addition of metformin, sulphonylureas, glinides, α-glucosidase inhibitors, thiazolidinediones and/ or exogenous insulin are recommended as the present treatment options. These treatments offer improvement in glycemic control, but in many instances produce significant adverse side effects. Various novel incretin-based therapies like prolonging GLP-1 receptor agonists action, orally GLP-1 receptor agonists, GLP-1 secretion by activating GLP-1-producing intestinal L-cells, synthetic engineered peptides as co-agonists stimulating more than one receptor, etc. are discussed here. I also present our experiences regarding development of successful gene therapy using intestinal K-cells which are specialized for GIP production. Engineering these cells to produce insulin in response to the ingested carbohydrates successfully achieved. Oral gene delivery to these cells using nanoparticles with appropriate protective coats as well as plant exosomal gene delivery to the stem cell precursors of K-cells located at the base of intestinal crypts resulted in long lasting insulin expression by gut K-cells and pronounced treatment of T2D.
Email: r_salehi@med.mui.ac.ir
