Khái niệm cốt lõi
Sex-specific kidney metabolism impacts diabetic kidney disease outcomes.
Tóm tắt
TOPLINE:
Sex-specific differences in kidney metabolism may underlie differences in diabetic kidney disease (DKD) outcomes in men and women.
METHODOLOGY:
Studies on proximal tubular epithelial cells (PTECs) from healthy male and female donors.
Analysis of mice with different sex chromosomes to identify metabolic differences.
Blood metabolomic analyses in adolescents and adults with or without diabetes and kidney disease.
TAKEAWAY:
Male PTECs showed increased mitochondrial respiration, oxidative stress, and apoptosis under high glucose.
Human male PTECs had increased glucose and glutamine fluxes to the TCA cycle.
Female PTECs showed increased pyruvate content.
Blood metabolomic analysis revealed differences in TCA cycle metabolites between males and females.
Serum pyruvate concentrations correlated with kidney function and mortality.
IN PRACTICE:
Investigate strategies to favor pyruvate accumulation and regulate TCA cycle activity.
SOURCE:
Led by Sergi Clotet-Freixas of University Health Network, Toronto, Canada, published in Science Translational Medicine.
LIMITATIONS:
Lack of patient-specific PTECs and differences in diabetes type between animals and humans.
DISCLOSURES:
Supported by various grants and funding sources, with some coauthors having received fees from industry.
Thống kê
PTECs from healthy male donors showed increased mitochondrial respiration, oxidative stress, and apoptosis under high glucose.
Serum pyruvate concentrations correlated with the estimated glomerular filtration rate and all-cause mortality.
Male sex and diabetes were associated with increased plasma TCA cycle metabolites, correlating with all-cause mortality.
Trích dẫn
"Strategies to favor pyruvate accumulation while preventing excessive TCA cycle activity should be investigated." - Authors