Comparative Aspects of Proinsulin and Insulin Structure and Biosynthesis

Abstract

This review summarizes currently available information on the composition and structure of vertebrate insulins and proinsulins. Consideration is given to the important structural features of insulin and its precursor that are involved in the function and formation of the active hormone. Studies on the biosynthesis of insulin in teleost fishes indicate the existence of larger single chain precursor forms similar to the mammalian proinsulins. Preliminary results of experiments on insulin biosynthesis in the hagfish ( Myxine glutinosa ), which has the most primitive islet parenchyma of all vertebrates, indicate the existence of a similar biosynthetic mechanism. The major storage product in the B-cells in all the vertebrate species studies thus far is insulin rather than proinsulin. In fishes an intracellular tryspin-like enzyme may suffice to convert proinsulin to insulin, while in mammals a more complex mechanism involving both an endopeptidase and an exopeptidase is probably required. Conversion occurs within the Golgi apparatus and newly formed secretory granules in the B-cells. The similarity to the higher vertebrates in the biosynthesis and molecular structure of insulin in the primitive hagfish indicates that the properties and biological role of this hormone have remained fairly constant throughout several hundred million years, or that its evolution has followed the same pattern in most extant organisms despite considerable differences in their origin and living conditions. A hypothesis for the evolution of insulin and of the B-cells based on the biosynthetic mechanism involving proinsulin and its conversion to insulin is briefly considered.