Mennickent, P. (Paula)

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    PPARGC1A gene promoter methylation as a biomarker of insulin secretion and sensitivity in response to glucose challenges
    (MDPI AG, 2020) Santos, J.L. (José Luis); Martinez, J.A. (José Alfredo); Riezu-Boj, J.I. (José Ignacio); Cataldo, L.R. (Luis R.); Salas-Huetos, A. (Albert); Mennickent, P. (Paula); Milagro-Yoldi, F.I. (Fermín Ignacio); Vega, J.A. (Javier Andrés); Arpon, A. (Ana); Prieto-Hontoria, P.L. (Pedro L.); Gallegos, R. (Raúl); Salas-Pérez, F. (Francisca); Krause, B.J. (Bernardo J.); Bravo, C. (Carolina); Galgani, J.E. (José E.)
    Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.