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.
Keywords: Insulin degradation, insulin-degrading enzyme, insulin action, insulin fragments, lipid metabolism, protein degradation.
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