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Abstract: SA-PO245

L-Lysine Dietary Supplementation Attenuates Hyperglycemia in Type 2 Diabetic Nephropathy Rats

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Kravtsova, Olha, University of South Florida, Tampa, Florida, United States
  • Isaeva, Elena, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Palygin, Oleg, Medical University of South Carolina Department of Medicine, Charleston, South Carolina, United States
  • Staruschenko, Alexander, University of South Florida, Tampa, Florida, United States
Background

Diabetic kidney disease (DKD) is one of the main complications of diabetes, leading to the progression of end-stage kidney failure. Recent studies provide evidence that dietary supplementation of the essential amino acid lysine significantly attenuates proximal tubule reabsorption and is critical for the regulation of kidney function. To explore the effect of lysine on hyperglycemia in the late stage of DKD progression, we used Type 2 Diabetic Nephropathy (T2DN) rats, a non-obese model of spontaneous development of diabetes, and similar renal injuries to clinical manifestation of DKD in humans.

Methods

Male T2DN rats (>48 weeks old) were kept on a Purina diet. L-lysine chloride or L-lysine acetate (91 mol/l) was supplied ad libitum in drinking water for 10 days. Fasting blood was collected from the tail vein, and glucose levels were determined with a glucometer. pH and electrolytes were measured with a blood gas analyzer. Plasma and kidney tissue were collected at the end of the experiment. RT-PCR and Western blotting were performed for mRNA and protein expression analysis.

Results

We found that L-lysine administration (chloride or acetate) attenuates hyperglycemia (197 ± 53 to 119 ± 10 after L-lysine chloride & 121 ± 6 to 73 ± 15 after L-lysine acetate, mg/dL glucose, p<0.01) in T2DN rats. mRNA expression of Slc5a2, the gene that encodes SGLT2, did not differ in both groups compared to untreated controls. Interestingly, chloride salt of lysine leads to acidosis compared to acetate (7.25 ± 0.02 vs. 7.46 ± 0.02 blood pH, respectively), probably due to increased Cl- supplementation. In comparison with untreated diabetic rats, lysine supplement leads to a lower abundance of transporters responsible for pH homeostasis. In particular, the expression of NHE3, and NBCe1 (only chloride group), mostly abandoned in proximal tubule cells, were decreased. Similarly, cortical collecting duct expression of V-ATPase B1/2 was reduced.

Conclusion

Our data suggest that essential dietary lysine supplementation results in a marked reduction of blood glucose in T2DN rats. That indicates that simple amino acid administration could be used for the treatment of hyperglycemia and type 2 diabetes complications.

Funding

  • Other NIH Support