Metabolic impact of host glucose homeostasis controlling hormones on the Echinococcus larval stage

NEGRO PERLA S.; LOOS JULIA .A.; DÁVILA VALERIA A.; CUMINO ANDREA C.

Lima

Congreso; XXVIII World Congress on Echinococcosis; 2019

Asociación Internacional de Hidatología y Ministerio de Salud de Perú

Glucose availability is essential to ensure development processes in Echinococcusgranulosus, both in definitive and intermediate hosts. Interestingly, the glucosemodulating drugs niclosamide and metformin have proven anticestodal activity inhuman and mice, respectively. Both drugs, with an excellent safety profile in mammals,induce mitochondrial uncoupling in treated cells, and can improve insulin sensitivityand suppress glucagon signaling in treated hosts. In order to contribute to theunderstanding of in vivo anthelmintic mechanisms of metformin and the parasite-hosthormonal interrelationship, we evaluated the metabolic activity of the parasite inpresence of glucagon, insulin and somatostatin, host hormones for which the cestodeexpresses putative receptors. Four glucose transporters (GLUTs, capable ofincorporating the 2-D-glucose fluorescent derivative) and two G-protein-coupledreceptors with high sequence identity to human glucagon and somatostatin receptorswere identified in the parasite larval stage. Although previous investigations have failedto demonstrate the gluconeogenesis in Echinococcus spp., we analyzed thetranscriptional expression of glucose-6-phosphatase, fructose-1, 6-bisphosphatase,phosphoenolpyruvate carboxykinase and malate dehydrogenase in hormone-treatedmetacestodes and protoscoleces. In presence of exogenous insulin and glucagon,antagonistic effects in relation to glycogen content, free glucose levels and glycolyticflux were recorded in the parasite. While in response to glucagon, glycogenolysis andmitochondrial activation were induced in calcareous corpuscles, in presence of insulin,glycogen accumulation and AKT-TOR pathway activation were evidenced. Thissuggests that the parasite responds to host neuroenteropancreatic hormones. Thesepeptide hormones may promote the parasite glucose homeostasis, necessarily requiredin the strobilar and vesicular development during the establishment of primary andsecondary echinococcosis, respectively.