Diabetes mellitus and other pathology in patients with INS and INSR mutations

Abstract

Over 20 missense mutations and Y108X nonsense mutation in INS are dominant and induce synthesis of chimeric proteins that may interfere with folding and processing of all insulin molecules. In heterozygous state they cause insulin deficiency and PND. Over 10 recessive mutations and the p.Q62X nonsense mutation of INS do not induce synthesis of anomalous protein, being associated with PND only in homozygous state. Most of significant mutations that induce insulin resistance, lipodystrophy, and other pathology were found in INSR gene. Lipodistrophy suggests an important role of insulin in stimulating fat accumulation and controlling lipid consumption in energy metabolosm.