Insulin Action at the Molecular Level: Facts and Speculations

Abstract

Insulin is a hormone that is itself anabolic and is required for the action of other major mammalian hormones that promote growth. Three groups of molecules possibly related to this anabolic function are considered: (1) molecules that relate to the structure of membranes and the initiation of insulin action, including insulin receptors; (2) molecules (such as cyclic nucleotides and cations, e.g. K+ and Mg++) that are potentially concerned with transmission and amplification of information from the plasma membrane to subcellular functional units; (3) molecules that may contribute directly to development of juvenile or maturity-onset diabetes. Two new concepts are proposed: First, the receptor for insulin occupies a locus on the plasma membrane coupled to Mg++-activated (Na+ + K+). ATPase; hormone activation stimulates ATPase activity. As a result of the activation of the membrane ATPase enzyme system by insulin, concentrations of K+ and Mg++ increase at critical intracellular loci; these ions then serve as “second messengers.” The second new concept is that the genetic abnormality in human diabetes mellitus lies in a single or multiple enzyme defect that leads to accumulation of a fragment from growth hormone. One such fragment is known to inhibit glucose uptake and fatty acid synthesis.