INS

About INS

INS on chromosome 11p15.5 encodes preproinsulin, which is processed in pancreatic beta cells into proinsulin and then into insulin and C peptide. Insulin is the central hormone of glucose regulation, promoting uptake of glucose into muscle and fat and storage of energy in the liver. Heterozygous INS variants that cause misfolding of proinsulin are an important cause of permanent neonatal diabetes, as the misfolded protein triggers endoplasmic reticulum stress and beta cell loss, and other INS variants cause diabetes later in childhood or rare forms of mutant insulin with abnormal blood levels. Unlike neonatal diabetes caused by KCNJ11 or ABCC8 variants affecting the KATP channel, INS related diabetes generally requires insulin treatment. A variable number tandem repeat in the INS promoter region influences susceptibility to type 1 diabetes, likely by affecting insulin expression in the thymus and immune tolerance. The gene is also near the imprinted region involved in Beckwith Wiedemann syndrome. Insulin was discovered in 1921 by Frederick Banting and Charles Best in Toronto, Frederick Sanger determined its amino acid sequence in the early 1950s, and in 1982 recombinant human insulin made in bacteria became the first approved drug produced by recombinant DNA technology.