Etiologia de la resistència a la insulina i anàlisi de gens candidats mitjançant mutagènesi dirigida

Study objective: Functional analysis of genes determining insulin sensitivity, and the contribution of mutations found in patients in the etiopathogenesis of insulin resistance. Design: Generation of knock-out mice for HKII and muscle GS genes, by targeting of embryonic stem cells. Interventions: Functional and estructural imnpact of mutation in the tissues where the gene is expressed. Effects of mutation in the intact animal, evaluation of insulin resistance, and the developement of related long-term processes (NIDM, cardiovascular disease, dyslipidemia, hypertension, obesity, etc.) Measurements: In these models, we will analyze the expression of the mutated and related genes, and metabolic parameters. Histopathology of organs and tissues, either expressing the mutation or altered by the mutation, will be performed. We will also carry out functional functional and clinical tests, glucose tolerance test, insulin sensivity, clinical monitorization, and specific tests of different organs in mutant mice.