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Abstract: TH-PO181

Kidney Tubule Specific AMPK α1 Knockout Abolishes Female Protection From Diabetes and Affects Amino Acid Metabolism in Diabetic Mice

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Lee, Hak Joo, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Gao, Jingli, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Min, Liang, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Ye, Hongping, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Franzone, Anthony J., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Ghosh-Choudhury, Goutam, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Kasinath, Balakuntalam S., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Group or Team Name

  • Center for Precision Medicine
Background

Reduced kidney AMPK activity is associated with progression of chronic kidney disease (CKD) which is ameliorated by AMPK stimulation in male mice, whereas female mice resist CKD from obesity and diabetes. Amino acids have been implicated in CKD but their mechanistic role is unclear. We hypothesized that kidney tubule specific deletion of AMPK catalytic α1 subunit abolishes female protection and dysregulates amino acid metabolism in diabetic mice.

Methods

3-4 month old kidney specific AMPK α1 knockout (KO) male and female mice (n=6-9 per group) were placed on normal fat diet or high fat diet (HFD) for 1 month, after which HFD groups received a low dose of streptozotocin. Urinary amino acids were measured by a targeted mass spectrometry platform.

Results

AMPK α1 expression was significantly reduced in the kidney of AMPK α1 KO mice without compensation by AMPK α2. Diabetes induced similar degree of hypertension and albuminuria in male WT and AMPK α1 KO mice. Female WT mice resisted diabetes-induced hypertension and albuminuria. In contrast, albuminuria and systolic blood pressure were elevated in female diabetic AMPK α1 KO mice. Diabetes increased urinary lysine level in male WT and AMPK α1 KO mice. Diabetes-increased urinary lysine level was not observed in female WT mice, but it was increased in female diabetic AMPK α1 KO mice. Urinary lysine level correlated with diabetes-induced albuminuria in male (p<0.001) and female (p<0.05) mice.

Conclusion

Female protection against diabetes is abolished in kidney tubule specific AMPK α1 KO mice. Our data indicate that AMPK plays a pivotal role in female protection and regulates lysine metabolism in diabetic mice. AMPK could be used for a therapeutic target of diabetes-induced kidney injury and dysfunction of lysine homeostasis.