Related Experiment Video
Updated: Jun 28, 2025
10:37
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
144
Female Protection Against Diabetic Kidney Disease Is Regulated by Kidney-Specific AMPK Activity
Hak Joo Lee1,2, Liang Min1, Jingli Gao1
1Center for Precision Medicine, Division of Nephrology, University of Texas Health, San Antonio, TX.
Diabetes
|April 24, 2024
Summary
Female mice are protected from nutrient stress-induced kidney disease, likely through an estrogen-AMPK pathway. This pathway involves specific metabolite changes and offers evolutionary advantages during nutrient challenges.
Area of Science:
- Nephrology
- Endocrinology
- Metabolomics
Background:
- Reduced kidney AMP-activated protein kinase (AMPK) activity is linked to nutrient stress-induced chronic kidney disease (CKD) in males.
- Female mice exhibit inherent resistance to nutrient stress-induced CKD.
Purpose of the Study:
- To investigate the role of kidney AMPK in sex-specific organ protection against nutrient stress.
- To evaluate the impact of metabolite changes on kidney protection in diabetic mice with tubule-specific AMPKγ2 knockout (KTAMPKγ2KO).
Main Methods:
- Utilized kidney tubule-specific AMPKγ2 knockout (KTAMPKγ2KO) male and female mice models.
- Administered diabetes induction and analyzed kidney injury markers, hypertension, and molecular signaling.
- Conducted RNA sequencing and metabolomic analysis to identify metabolite changes.
- Investigated the effect of 17β-estradiol on kidney tubule cells.
Main Results:
- In wild-type males, diabetes exacerbated kidney injury markers, but this was not worsened by KTAMPKγ2KO.
- While wild-type females were protected, KTAMPKγ2KO led to a loss of this protection.
- 17β-estradiol ameliorated high glucose-induced AMPK inactivation and matrix accumulation in kidney tubule cells.
- A decrease in phenylalanine and tyrosine degradation pathways was observed in females, correlating with protection loss.
Conclusions:
- Female protection against diabetic kidney injury is mediated by an estrogen-AMPK pathway.
- Metabolite alterations, specifically in phenylalanine and tyrosine degradation, are linked to protection.
- Findings suggest evolutionary advantages for females during nutrient challenges via this pathway.
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