Insulin Signalling Lab

A major factor in the development of type 2 diabetes is the insulin resistance of tissues such as liver and skeletal muscle. Although the mechanisms involved are not fully understood, there is a close association between insulin resistance and increased lipid availability. Our lab has previously identified the roles played by protein kinase C (PKC) and specific inhibitory lipid intermediates, especially the sphingolipid ceramide.

We employ in vivo models and knockout mice, as well as cell culture systems and proteomic and lipidomic technologies, to investigate novel pathways and identify new strategies for type 2 diabetes therapies. We also pursue the translation of our findings into clinical settings, using novel or existing drugs that target PKCs and inhibitory lipids to improve glucose homeostasis.

Our research goals are:

1. To define the interactions between PKC, lipid metabolism and insulin action.

Our research has shown that the currently-held view that PKCs act solely to suppress proximal insulin signal transduction is an oversimplification. We will extend our novel findings, which show that these kinases and their specific downstream mediators play key roles in the control of lipid storage and oxidation in liver, and other insulin target tissues. This work will have relevance not only to diabetes but also hepatic steatosis, cardiovascular disease and the metabolic syndrome.

2. To examine the effectiveness of targeting key molecules for the treatment of diabetes, using new and existing drugs. We will further pursue the translation of our basic research findings into clinical settings. We will test existing inhibitors of PKC isoforms in vivo and in vitro, to determine their effectiveness in improving insulin action. Because of specificity problems with targeting kinase catalytic activity, we have also initiated a project to generate novel PKC inhibitors using other strategies.