A Genetic Strategy to Measure Circulating Insulin Reveals Genes Regulating Insulin Production and Secretion

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Genome-wide association studies in patients with type 2 diabetes mellitus have identified more than 65 loci, encoding up to 500 candidate susceptibility genes. Thus, investigators are fundamentally challenged to (i) screen and identify relevant candidates in vivo, (ii) determine if loss- or gain-of-function underlies the association, (iii) link perturbed gene function to hallmark type 2 diabetes mellitus physiological phenotypes like insulin production or secretion, and (iv) identify relevant tissue(s) where the biological function of a specific regulator is required. Here we exploit Drosophila genetics to reveal the molecular functions of evolutionally conserved regulators that are associated with human type 2 diabetes mellitus. Targeted knockdown of Drosophila orthologues of diabetes risk genes revealed tissue-specific roles for these genes in regulating insulin production and secretion. These findings should accelerate use of Drosophila and other genetically-tractable systems to discover conserved mechanisms and regulators controlling in vivo insulin dynamics relevant to diabetes and other human diseases.

Vyšlo v časopise: A Genetic Strategy to Measure Circulating Insulin Reveals Genes Regulating Insulin Production and Secretion. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004555
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004555

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