PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges
(2020) In Nutrients 12(9). p.1-15- Abstract
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,... (More)
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.
(Less)
- author
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- keywords
- Adult, Biomarkers/blood, Blood Glucose, Chile, DNA Methylation/genetics, Female, Humans, Insulin Resistance/genetics, Insulin Secretion/genetics, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics, Promoter Regions, Genetic/genetics
- in
- Nutrients
- volume
- 12
- issue
- 9
- article number
- 2790
- pages
- 1 - 15
- publisher
- MDPI AG
- external identifiers
-
- pmid:32933059
- scopus:85090659603
- ISSN
- 2072-6643
- DOI
- 10.3390/nu12092790
- language
- English
- LU publication?
- no
- id
- b87b1763-8f3a-4c92-ac7a-8ce7f88055df
- date added to LUP
- 2022-02-01 07:36:57
- date last changed
- 2024-06-29 01:47:11
@article{b87b1763-8f3a-4c92-ac7a-8ce7f88055df, abstract = {{<p>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.</p>}}, author = {{Santos, José L and Krause, Bernardo J and Cataldo, Luis Rodrigo and Vega, Javier and Salas-Pérez, Francisca and Mennickent, Paula and Gallegos, Raúl and Milagro, Fermín I and Prieto-Hontoria, Pedro and Riezu-Boj, J Ignacio and Bravo, Carolina and Salas-Huetos, Albert and Arpón, Ana and Galgani, José E and Martínez, J Alfredo}}, issn = {{2072-6643}}, keywords = {{Adult; Biomarkers/blood; Blood Glucose; Chile; DNA Methylation/genetics; Female; Humans; Insulin Resistance/genetics; Insulin Secretion/genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics; Promoter Regions, Genetic/genetics}}, language = {{eng}}, number = {{9}}, pages = {{1--15}}, publisher = {{MDPI AG}}, series = {{Nutrients}}, title = {{PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges}}, url = {{http://dx.doi.org/10.3390/nu12092790}}, doi = {{10.3390/nu12092790}}, volume = {{12}}, year = {{2020}}, }