Insulin (INS) Active Protein

After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

Function: Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.

Subunit structure: Heterodimer of a B chain and an A chain linked by two disulfide bonds.

Subcellular location: Secreted.

Involvement in disease: Hyperproinsulinemia, familial (FHPRI) [MIM:176730]: An autosomal dominant condition characterized by elevated levels of serum proinsulin-like material.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.23 Ref.24 Ref.25Diabetes mellitus, insulin-dependent, 2 (IDDM2) [MIM:125852]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.34Diabetes mellitus, permanent neonatal (PNDM) [MIM:606176]: A rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.32 Ref.33Maturity-onset diabetes of the young 10 (MODY10) [MIM:613370]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.33 Ref.34 Ref.35

Pharmaceutical use: Available under the names Humulin or Humalog (Eli Lilly) and Novolin (Novo Nordisk). Used in the treatment of diabetes. Humalog is an insulin analog with 52-Lys-Pro-53 instead of 52-Pro-Lys-53.

Sequence similarities: Belongs to the insulin family.

Sequence caution: The sequence AAA59179.1 differs from that shown. Reason: Erroneous gene model prediction.