Jitendra Kumar, Anjali Awasthi2, Kyung-Chae Park, Vijay Kumar Singh and Birendra Prasad
Many pharmacological drugs have been reported to alter insulin signalling in the body resulting in altered blood glucose levels. Drug induced hypoglycaemic or hyperglycaemic effect may lead to adverse effects especially in diabetic patients. Treating ailments of diabetic patients has always remained challenging for the clinicians due to unexplored effect of many drugs on insulin signalling. Insulin/insulin like growth factor-1 signalling (IIS) pathway is highly conserved between Caenorhabditis elegans and humans. In both C. elegans and humans IIS pathway is involved in regulating fat storage. C. elegans dauer formation is regulated primarily via IIS pathway and is triggered by adverse environmental conditions. In this paper we proposed the use of C. elegans dauer formation as a vital strategy to check the drug interaction with IIS. Activity of DAF-2 and DAF-16 are the key regulators of IIS in C. elegans. Aspirin, silymarin and pravastatin drugs have been reported to alter blood glucose levels using animal models and clinical reports. To test the efficacy of our model we tested the effect of these drugs on IIS by using dauer formation as a read-out. Our results report that aspirin and silymarin decreased dauer formation whereas pravastatin enhanced it; the effect was mediated through daf-16 signalling. Our results thus report that C. elegans dauer formation can be used as an effective readout for drug and IIS pathway interaction.
