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Abstract: PO0682

The Molecular Effect of the Sodium-Glucose Transporter 2 (SGLT-2) Inhibitor Empagliflozin on the Autophagy Pathway in Diabetes Mellitus and Its Vascular Complications

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Saad, Ranin, Diabetes Metabolism Lab Azrieli faculty of Medicine Bar Ilan University, Bar-Ilan, Israel
  • Farber, Evgeny, Nephrology Division Baruch padeh Poriya Medical Center, Tiberias, Israel
  • Nakhoul, Rola, Erlangen Univerity Hospital Anästhesiologische Klinik, Erlangen, Germany
  • Ertracht, Offir, Galilee Medical Center, Nahariya, Israel
  • Nakhoul, Farid M., Galilee Medical Center, Nahariya, Israel
  • Tadmor, Hagar, Diabetes Metabolism Lab Azrieli faculty of Medicine Bar Ilan University, Bar-Ilan, Israel
Background

Diabetes mellitus (DM) is a severe metabolic disorder characterized by chronic hyperglycemia. DM is associated with increased oxidative stress that can lead to irreversible kidney damage and kidney failure. Empagliflozin (EMPA) is a novel anti-diabetic drug, known as SGLT2i in T2DM patients. Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary or dysfunctional intracellular components, and is known to have an important role in DM complication (Diabetic Nephropathy-DN). We aim to investigate the protective role of EMPA treatment on DN via the autophagic proteins ATG5 & LC3B.

Methods

We used T2DM animal model-mouse strain BTBR with the ob/ob leptin-deficiency mutation that develops severe type II DM which is presented with hyperglycemia and DN. EMPA will be administrated to the diabetic mice via drinking water for a period of 12 weeks. Routine monitoring of blood and urine standard DM parameters will be carried through experiment duration. At the end of the experiment, mice kidneys will be removed and subjected to further biochemical and histological analysis: Western blot analyses, Immunohistochemistry staining will be performed to evaluate ATG5, LC3B, level and expression.

Results

Blood glucose concentration was normal in control mice(C57) throughout the experiment. In DM mice (BTBR) without EMPA, blood glucose concentration was higher than control, and lower in diabetic mice treated with EMPA compared to DM. Urine volume of BTBR mice treated with EMPA increased throughout the experiment and was higher in comparison to DM mice without EMPA treatment.
Renal cortical expression of ATG5 were 6.83±0.52%, 2.59±0.54% and 6.29±.74% for the C57, DM and DM+EMPA, respectively (P<0.001 vs. DM for both)) and LC3B were 9.60±2.14%, 3.19±0.66% 7.39±1.74% in the C57, DM mice and DM+EMPA, respictevely (P<0.001 between all groups.

Conclusion

1. EMPA Treatment induces glucosuria and body weight reduction in diabetic mice model
2. Chronic Hyperglycemia down regulates the expression of LC3 & ATG5, the two main proteins in the autophagy process.
3. Treatment EMPA for 12 weeks restore the the expression of these proteins in the kidney
4. EMPA can be first line treatment in type II DM patients to slow the progression of DN..