title: Biologically active insulin-derived peptides.
abstract: Insulin has many actions within cells many of which are dependent on the cell type. For example, insulin stimulates glucose uptake in adipose tissue and skeletal muscle but not in liver. In liver glucose influx will increase as insulin stimulates the phosphorylation of glucose and eventual storage in the form of glycogen. Insulin also increases glucose oxidation, decreases glucose production, decreases lipolysis, increases protein synthesis and inhibits protein degradation in addition to others. Many actions have been related to insulin binding to its receptor and subsequent phosphorylation cascades, but insulin action on protein degradation has been shown to be linked to insulin degradation, specifically insulin degradation by the insulin-degrading enzyme (IDE). This activity has been shown to be due to an interaction of IDE with the proteasome, which is responsible for degradation of ubiquitin-tagged proteins. Smaller fragments of insulin that are produced by the action of IDE that do not bind to the insulin receptor show a small effect on protein degradation and a modest effect on mitogenesis. These small fragments do however inhibit lipolysis in a similar manner to insulin. If fragments are larger and can bind to the receptor they have been shown to increase glucose oxidation. Studies show that fragments of the insulin molecule have cellular activity, and that the varied actions of insulin are not completely controlled by insulin binding to the insulin receptor, even though the mechanisms may not be mutually exclusive.
authors.affiliation: Phoenix VA Health Care System, Endocrinology (CS/111E), 650 E. Indian School Road, Phoenix, AZ 85012, USA. janet.fawcett@va.gov.
authors.forename: Janet
authors.initials: J
authors.lastname: Fawcett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D007328:Insulin; D010446:Peptide Fragments