Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

The effect of niclosamide on suppressing glucagon action in the liver (#209)

Greg Smith 1
  1. UNSW Sydney, Eastlakes, Sydney, NSW, Australia

Type 2 diabetes (T2D) and the complications associated with this metabolic disease are increasing globally. The current drug treatment options do not target the underlying cause of this disease and most people will end up on insulin replacement therapy due to drug complications and disease progression. Newer drugs with well-defined mechanism of action that target the cause of the metabolic alterations are urgently needed. People with T2D have increased liver glucose production and release that is largely driven by a hormone that is elevated in this disease called glucagon. We have recently identified that glucagon increases liver glucose production by activating a protein called beta-catenin. Interestingly, a group from the USA showed that a common worm drug called niclosamide decreased liver glucose metabolism by altering mitochondrial function. But niclosamide is also known to reduce the activity of beta-catenin. So, we set up experiments in primary liver cells, isolated rat livers and in whole animal models and found that niclosamide decreased liver glucose production and improved glucose metabolism by blocking beta-catenin activity. Thus, we have convincing evidence that niclosamide can block the action of glucagon, in the liver that improves glucose metabolism in a range of models tested.