An MG53-IRS1-interaction disruptor ameliorates insulin resistance

Abstract

Diabetes: lowering glucose levels by targeting protein interactions A promising drug candidate for type II diabetes targets a protein interaction involved in insulin resistance. In healthy individuals, the insulin receptor substrate 1 (IRS-1) protein stimulates glucose uptake, particularly in skeletal muscles. In patients with diabetes, the interaction of IRS-1 with another protein, MG53, interferes with insulin signaling and causes insulin resistance, resulting in excess glucose in the blood. Drugs for treating diabetes aim to lower glucose levels, but no existing drugs directly target glucose levels in skeletal muscles. Now, Bong-Woo Kim and Young-Gyu Ko at Korea University in Seoul, South Korea, and co-workers have designed a drug that specifically inhibits the IRS-1-MG53 interaction. Oral administration of the drug showed promise in trials on diet-induced obese mice, increasing IRS-1 levels in skeletal muscles, lowering fasting glucose levels and improving insulin sensitivity.