Molecular Physiology of Insulin Function

Abstract

Insulin is a peptide hormone that is secreted by the pancreatic β-cells and it plays a pivotal role in a number of cellular metabolic processes. Structurally, it consists of two chains that are connected by disulphide bonds. It is secreted from the β-cells upon membrane depolarization and opening of potassium sensitive ATP channels. This process can be initiated by several stimuli especially glucose entry into the cell. Insulin signal transduction starts with binding of the receptor which belongs to the tyrosine kinase family and phosphorylation of Insulin Receptor Substrates. Consequently, two well defined pathways i.e. the phosphoinositide-3-kinase which is involved in carbohydrate, lipid and protein metabolism as well as the MAP-kinase pathway which mediates mitogenesis are established. Insulin enhances glycolysis and glycogenesis while inhibiting gluconeogenesis and glycogenolysis. It also promotes lipogenesis and inhibit lipolysis. These effects are possible because of its ability to activate and deactivate several enzymes and other substrates via phosphorylation. It is also involved in the induction of genes coding for important enzymes in these pathways. The effects of insulin extend to the regulation of vascular structure and function partly through its ability to stimulate nitric oxide production. The aim of this article is to summarize the molecular mechanisms behind the most important insulin functions.