SAT-LB033 Cryptolepine Action on Insulin Resistance in High-Glucose Diet-Fed Caenorhabditis Elegans

Cryptolepine, a pharmacologically active plant alkaloid, is isolated from the roots of the shrub Cryptolepis sanguinolenta commonly found in the Central and Western regions of the African continent. Cryptolepine exhibits significant potential as an anti-malarial, anti-bacterial, anti-inflammatory and anti-hyperglycemic agent under different in vitro and in vivo conditions. At present, relatively few studies on the effects of cryptolepine on development of insulin resistance, a pre-diabetic condition, have been reported. High-glucose diets (HGD) cause a rapid increase in blood glucose level and alter glucose homeostasis by inducing insulin resistance in organisms as diverse as yeasts, worms, and mammals. In the present study, we hypothesize that cryptolepine will prevent development of insulin resistance by its anti-inflammatory action in HGD-fed Caenorhabditis elegans (C. elegans) worms. To test the hypothesis, we examined the modulation of insulin resistance and oxidative-stress induction and associated regulatory mechanisms by cryptolepine in HGD-fed C. elegans. Initially, we investigated fat accumulation and survival (development, fertility and lifespan) in three types of C. elegans: wild-type worms, HGD-fed high-fat worms cultured in nematode growth medium containing 10 mM glucose and C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1) receptor mutant worms in which metabolism is shifted towards fat accumulation. Next, we determined the expression of genes involved in immune-signaling pathways, particularly, dbl-1, and the daf-2/daf-16 pathways that could be responsible for the development of insulin resistance and oxidative-stress induction in these worms. Finally, we treated all three types of C. elegans with cryptolepine to investigate whether it prevents fat accumulation and rescues the worms from insulin resistance and oxidative stress. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.