Screening for Insulin-Like/Mimetic Drugs Using Lower Eukaryotes

Abstract

It has generally been assumed that hormones and the corresponding intra-and intercellular signal transduction pathways and mechanisms have evolved exclusively during course of the evolution of vertebrate endocrine organs, implying a rather recent origin. However, there is good experimental evidence for (i) the expression of hormones and hormone-binding proteins resembling those of vertebrates in fungi and yeast, (ii) functional responses of lower eukaryotes to mammalian hormones and (iii) the existence of components of insulin-like and mimetic signaling pathways as well as their coupling to G-protein coupled receptors and metabolic pathways, such as lipolysis and endoplasmic reticulum stress, in lower eukaryotes, in particular in Neurospora crassa and Saccharomyces cerevisiae. Data will be presented that the naturally occurring or recombinant expression of insulin-like/mimetic signaling pathways in lower eukaryotic cells may be useful as model systems for future drug screening and discovery efforts.