安普克
肾
医学
肾脏疾病
糖尿病
疾病
内科学
内分泌学
生物
细胞生物学
蛋白激酶A
激酶
作者
Hak‐Joo Lee,Min Liang,Jingli Gao,Shane Matta,Viktor R. Drel,Afaf Saliba,Ibón Tamayo,Richard Montellano,Leila Hejazi,Soumya Maity,Guogang Xu,Brian Grajeda,Sourav Roy,Kenneth R. Hallows,Goutam Ghosh Choudhury,Balakuntalam S. Kasinath,Kumar Sharma
标识
DOI:10.2337/figshare.25668735.v1
摘要
<p dir="ltr">Reduced kidney AMPK activity is associated with nutrient stress-induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress-induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes were evaluated in diabetic kidney tubule-specific AMPKg2KO (KTAMPKg2ΚΟ) male and female mice. In WT males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKg2ΚΟ. Whereas WT females had protection against diabetes induced kidney injury, KTAMPKg2ΚΟ led to loss of female protection against kidney disease. 17b-estradiol ameliorated high glucose-induced AMPK inactivation, p70S6K phosphorylation and matrix protein accumulation in kidney tubule cells.<b> </b>The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA-seq and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges.</p>
科研通智能强力驱动
Strongly Powered by AbleSci AI