title: Sex differences in skeletal muscle phosphatase and tensin homolog deleted on chromosome 10 (PTEN) levels: a cross-sectional study.
abstract: Women have higher adiposity but maintain insulin sensitivity when compared to men. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibits insulin signaling, but it is not known if PTEN regulate insulin resistance in a sex-specific manner. In this cross-sectional study, muscle biopsies from participants in the Molecular Study of Health and Risk in Ethnic Groups (Mol-SHARE) were used to test for sex differences in PTEN expression. Quantitative real-time PCR was performed to determine PTEN gene expression (n = 53), and western blotting detected total and phosphorylated PTEN protein (n = 36). Study participants were comparable in age and body mass index. Women had higher fat mass percentage compared to men (40.25 ± 9.9% in women versus 27.6 ± 8.8% in men; mean difference -0.18, 95%CI (-0.24, -0.11), p-value <0.0001), with similar HOMA-IR (2.46 ± 2.05 in men versus 2.34 ± 3.06 in women; mean difference 0.04; 95% CI (-0.12, 0.21), p-value 0.59). Women had significant downregulation of PTEN gene expression (p-value 0.01) and upregulation of PTEN protein phosphorylation (inactivation) (p-value 0.001) when compared to men after correction for age, ethnicity, HOMA-IR, fat mass and sex. We conclude that the downregulation of muscle PTEN may explain the retention of insulin sensitivity with higher adiposity in women compared to men.
authors.affiliation: 1] Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada [2] Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada.
authors.forename: M Constantine
authors.initials: MC
authors.lastname: Samaan
authors.affiliation: 1] Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada [2] Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada [3] Department of Medicine, McMaster University, Hamilton, Ontario, Canada [4] Department of Clinical Epidemiology/Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
authors.affiliation: 1] Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada [2] Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Samjoo
authors.affiliation: 1] Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada [2] Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000378:metabolism; D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009929:Organ Size; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D051059:PTEN Phosphohydrolase