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Abstract: PO0698

Female Protection Against Diabetes-Induced Kidney Injury Is Eliminated in Kidney Tubule-Specific AMPK Gamma-2 Knockout Mice

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Min, Liang, 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
  • Lee, Hak Joo, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Xu, Guogang, 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
Background

Reduction in renal AMPK activity is associated with obesity- and diabetes-induced kidney injury which is ameliorated by AMPK stimulation in male mice. Female mice resist obesity-induced kidney injury; this protection is abolished in kidney tubule specific α1 and α2 KO female mice. We tested if interruption of AMPK activity abolishes renal protection against diabetes in AMPK γ2 KO female mice. We also tested if diabetes worsens kidney injury in AMPK γ2 KO male mice.

Methods

3-4 month-old tubule-specific AMPK γ2 KO male and female mice (n= 6-9 per group) were employed. To generate diabetic animal model, the mice were placed on high fat diet (HFD) for one month, then they received streptozotocin (STZ) 50mg/kg body weight by IP daily for 5 days. After 1 month STZ injection, urine was collected for analyzing urinary KIM-1 and ACR.

Results

Renal cortical expression of AMPK γ2 mRNA as well as protein was reduced in AMPK γ2 KO mice. There were no changes in body weight and random blood glucose level between control and AMPK γ2 KO male and female mice at the baseline. Body weight gain in control and AMPK γ2 KO mice in both genders was increased by HFD compared to normal fat diet fed groups. Random blood glucose level was increased in HFD and STZ-treated control and AMPK γ2 KO mice in both genders. As expected control female mice resisted HFD and STZ-induced kidney injury, whereas urinary KIM-1 excretion and albuminuria were increased in AMPK γ2 KO female mice. Urinary KIM-1 excretion and albuminuria were induced by diabetes in control and γ2 KO male mice with no statistical difference between two groups.

Conclusion

Renal protection against diabetes is abolished in kidney tubule specific AMPK γ2 KO female mice. Therefore, regulation of AMPK as well as its activity contributes to the protective mechanism against diabetes in female mice, and it could be used for a therapeutic target of diabetes.