All data were normalized to total lean mass using the EchoMRI 100 quantitative magnetic resonance method as described previously. In the present paper we report pharmacokinetic information for PI 103, TGX221 and IC87114 following oral or intraperitoneal injection. These studies established that the intraperitoneal dose of 10 mg/kg of body mass gave ideal blood levels of drug for short term metabolic studies. The outcome of the current study show that the pan PI3K/mTOR inhibitors PI 103 and BEZ235, and the pan PI3K chemical ZSTK474 greatly reduced whole natural product libraries human body glucose metabolism in mice. The finding the drugs induced significant impairments in insulin tolerance suggests they’re causing insulin resistance at the amount of one or most of the major insulin target cells, i. e. muscle, liver or fat. The finding that each of them increased production of glucose from pyruvate in a PTT shows that gluconeogenesis is increased and provides evidence that insulin action in the liver is impaired. Further evidence that insulin resistance is induced by the drugs comes from the GTT results which show that all three of these pan PI3K inhibitors induced significant problems in the capability of the mice to get rid of a glucose load. Of the isoformselective Chromoblastomycosis type IA PI3K inhibitors, PIK75 and A66 induced significant problems in the ITT and GTT, and a growth in sugar production during a PTT, with IC87114 and TGX221 having only minimal effects. AS252424 caused a significant upsurge in hepatic glucose production and a tendency towards an impairment in insulin tolerance. AS252424 was initially described as a p110 selective inhibitor, however the results above lead us to re evaluate this and we find that it checks p110 with an IC50 value of 17 nM and p110 with an IC50 value of 80 nM. Therefore in vivo this inhibitor probably will be cross reacting with p110. One possible explanation for defects in glucose metabolism could be an inhibitory influence on insulin release therefore results have already been reported previously in vitro. Nevertheless, insulin levels didn’t decrease in the drug treated animals throughout the GTT. In fact insulin ALK inhibitor levels increased in the case of the container PI3K inhibitors and PIK75 and A66, in line with the impaired glucose tolerance aswould be likely in a insulin resistant state. Therefore, although a little effect on insulin release can not be eliminated, the drugs undoubtedly dont fully block insulin release. We were also interested to investigate whether acute administration of those PI3K inhibitors may influence energy expenditure and so we performed metabolic cage reports. These studies did not discover any changes in BMR or oxygen consumption. Neither have there been important changes in water use. But, BEZ235 induced significant reductions in food intake in both the light and dark cycle, whereas PI 103 and PIK75 caused significant decreases in food intake during the light cycle. During the metabolic cage studies, information were also obtained on animal movement.