PPARGC1A gene promoter methylation as a biomarker of insulin secretion and sensitivity in response to glucose challenges

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/sensitivi...

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Autores: Santos, J.L. (José Luis)|||/items/b14e2212-42c2-440a-a236-430df8446638, Krause, B.J. (Bernardo J.)|||/items/3a749511-3128-4b1c-9c53-61cde7e7c3a4, Cataldo, L.R. (Luis R.)|||/items/2f41b90a-4277-402e-9da2-71d8c7194ba0, Vega, J.A. (Javier Andrés)|||/items/63765799-5090-4d57-93ae-d240f4fd50a8, Salas-Pérez, F. (Francisca)|||/items/60f268d1-df7d-40f1-8880-272903343a37, Mennickent, P. (Paula)|||/items/19a07304-6787-4aa6-8c85-1d40ac2bfa32, Gallegos, R. (Raúl)|||/items/62e367e5-63e1-4063-847b-cb1dddc94c31, Milagro-Yoldi, F.I. (Fermín Ignacio)|||/items/07cf7af6-1f5f-4720-8c14-5197a7a724eb, Prieto-Hontoria, P.L. (Pedro L.)|||/items/74b9fcba-d3ed-4a1c-8979-86b8359cb6c7, Riezu-Boj, J.I. (José Ignacio)|||/items/87349e89-7360-4cdd-81be-2e8a6174b5f6, Bravo, C. (Carolina)|||/items/3243a990-7625-4666-b20a-efd2a2be95e8, Salas-Huetos, A. (Albert)|||/items/f6375d33-94e9-4ca9-93be-6010e7adb674, Arpon, A. (Ana)|||/items/e1ea7066-dbdf-42e3-b6a9-b9f5c86adc2f, Galgani, J.E. (José E.)|||/items/547e4962-3a7f-4d6d-ac5c-c93440270723, Martinez, J.A. (José Alfredo)|||/items/6a3581ea-897b-4439-a95c-19301775e131
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/67698
Acceso en línea:https://hdl.handle.net/10171/67698
Access Level:acceso abierto
Palabra clave:Methylation
Insulin sensitivity
Insulin secretion
Biomarker
Gene variant
PPARGC1A gene
Descripción
Sumario: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.

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