Sensitizing Aptamer INSR‐A43 Enhances Insulin Sensitivity and Sensitizes Insulin Receptor Signaling Pathways

Abstract

Aptamers are single‐stranded oligonucleotides (DNA or RNA) and form a unique three‐dimensional (3D) structure based on its sequence. These aptamers have high affinity and specificity to target molecule and recognize 3D structure of target molecule surface. For this reason, aptamers have been in the spotlight as a universal capture. Especially, aptamers can modulate target protein as allosteric agonist or allosteric antagonist. However, aptamer‐based allosteric enhancer or sensitizer (hereafter ‐ sensitizer) has not been elucidated. Here, for the first time, we show the INSR‐A43, which is aptamer‐based sensitizer for the insulin receptor. Because insulin receptor plays a key role in regulation of glucose metabolism, it is important to specifically modulate the insulin receptor. INSR‐A43 binds to allosteric site of the insulin receptor and then increases insulin binding to the insulin receptor. Taken together, INSR‐A43 effectively enhances insulin sensitivity to the insulin receptor and sensitizes insulin receptor and insulin receptor‐related downstream signaling pathways. We expect that aptamers can be applied as an attractive tool for receptor sensitization.Support or Funding InformationThis research was supported by Grobal Research Laboratory (GRL) Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (No. NRF‐2016K1A1A2912722)