TY - JOUR
T1 - PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges
AU - Santos, José L
AU - Krause, Bernardo J
AU - Cataldo, Luis Rodrigo
AU - Vega, Javier
AU - Salas-Pérez, Francisca
AU - Mennickent, Paula
AU - Gallegos, Raúl
AU - Milagro, Fermín I
AU - Prieto-Hontoria, Pedro
AU - Riezu-Boj, J Ignacio
AU - Bravo, Carolina
AU - Salas-Huetos, Albert
AU - Arpón, Ana
AU - Galgani, José E
AU - Martínez, J Alfredo
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Adult
KW - Biomarkers/blood
KW - Blood Glucose
KW - Chile
KW - DNA Methylation/genetics
KW - Female
KW - Humans
KW - Insulin Resistance/genetics
KW - Insulin Secretion/genetics
KW - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
KW - Promoter Regions, Genetic/genetics
U2 - 10.3390/nu12092790
DO - 10.3390/nu12092790
M3 - Article
C2 - 32933059
SN - 2072-6643
VL - 12
SP - 1
EP - 15
JO - Nutrients
JF - Nutrients
IS - 9
M1 - 2790
ER -
