INSULIN SIGNALING IN THE YEAST SACCHAROMYCES-CEREVISIAE - 1 - STIMULATION OF GLUCOSE-METABOLISM AND SNF1 KINASE BY HUMAN INSULIN

Effects of human insulin on glucose metabolism in the yeast Saccharomy ces cerevisiae were studied in this report. Under two conditions of gr owth limitation (glucose-grown cells during transition to stationary p hase or spheroplasts during incubation in synthetic glucose medium), h uman insulin (10 and 1 mu M, respectively) enhanced glycogen accumulat ion and glycogen synthase activity by 40-60% compared to control cells . Glycogen phosphorylase activity was also increased under the same co nditions, but this stimulation was diminished by 35-45% in insulin-tre ated compared to control cells. Thus, under growth limitation, insulin causes glycogen phosphorylase and glycogen synthase to become more se nsitive to inactivation and activation, respectively. In glucose-induc ed spheroplasts, insulin (1 mu M), in addition to glycogen accumulatio n, led to about 2-fold increases of the rates of ethanol production an d glucose oxidation compared to control cells, and the maximal concent ration of hexose 6-phosphate was increased by 30-40%. In contrast, glu cose transport as well as the levels of the allosteric regulators, fru ctose 2,6-bisphosphate and cAMP, were not altered at all. Snf1 kinase is assumed to be involved in the regulation of glycogen metabolism in yeast, although it does not seem to be modulated directly by the gluco se concentration. Snf1 kinase activity was elevated 5-10-fold in respo nse to insulin both during glucose induction of yeast spheroplasts and during transition to stationary phase of glucose-grown cells. We conc lude that Saccharomyces cerevisiae and insulin-sensitive mammalian cel ls share some parts of the signaling cascades regulating oxidative and nonoxidative glucose metabolism in response to glucose and insulin.