Deepti Arha, E Ramakrishnab, Rakesh Mauryab and A K Tamrakara
Central Drug Research Institute, India
Worldwide occurrence of insulin resistance is around 20% of human population and it is primarily linked to type 2 diabetes. Insulin resistance is associated with blunted response of insulin in peripheral tissues like skeletal muscle, adipose tissue and liver. Therapeutic approaches with natural product lay an excellent foundation for search of effective, relatively safe and inexpensive treatment options for diabetes mellitus and associated metabolic disorders. In search of novel compounds to ameliorate insulin resistance, we synthesized a derivative of isoalantolactone that increase glucose uptake in skeletal muscle cells dose dependently through increasing the translocation of GLUT4 to the cell surface. Compound exhibit its effect by augmenting the phosphorylation of AMPK. Activation of downstream AMPK signaling was confirmed by enhanced phosphorylation of ACC and SREBP-1c. The compound significantly ameliorates TNFα-induced insulin resistance in L6 myotubes. Moreover, when studied by CLAMS in db/ db mice, it improved VO2, VCO2 and respiratory exchange ratio. There was a marked improvement in blood glucose as observed in oral glucose tolerance test. Treatment with the compound significantly increase energy expenditure by heat generation compared to control. There is an increase in mitochondrial genes like COX IV and cytochrome C. The compound significantly decreases serum cholesterol and increase clearance of triglyceride from the liver thus combating obesity induced insulin resistance and type 2 diabetes.
Deepti Arha has completed her Master’s in Microbiology and is pursuing her PhD from CSIR’s prestigious institute on Drug Research, CSIR-Central Drug Research Institute. She has qualified national exams for fellowship like CSIR-JRF, ICMR-JRF and Graduate Aptitude Test with 94 percentile. She has published five papers in international journals. Except working in drug development, she is also working in the field of Gut Dysbiosis and Insulin Resistance.
Email: deepti.arha@gmail.com
