Kidney Week

Abstract: SA-PO125

High Protein Diet and Potassium Depletion Exacerbate Ammonia Synthesis and Renal Hypertrophy in Rats with Type I Diabetes

Session Information

• Diabetic Kidney Disease: Basic - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Amlal, Hassane, University of Cincinnati, Cincinnati, Ohio, United States

Hassane Amlal,

• Amlal, Sihame, University of Cincinnati, Cincinnati, Ohio, United States

Sihame Amlal,

• Alam, Perwez, University of Cincinnati, Cincinnati, Ohio, United States

Perwez Alam,

Background

We have previously reported that the early onset of hyperglycemia stimulates ammoniagenesis, which contributes to the development of early renal hypertrophy in both type 1 (T1) and type 2 diabetes mellitus (DM) (ASN abstarct, 2017). In these studies, we examined whether other ammoniagenic conditions such as K⁺ depletion and high protein (HP) diet worsen renal hypertrophy in rat with T1 DM.

Methods

Male rats were housed in metabolic cages with free access to paired control diet and water and subjected to vehicle or streptozotocin (STZ)-induced DM. After 1 week, diabetic rats were divided into 3 groups: one group was switched to a K⁺-free (KD) diet (DM+KD), another group was switched to a HP diet (DM+HP) and the 3^rd group remained on normal diet for another week (DM). Vehicle-treated rats were fed control diet (control), K⁺-free or HP diets for 1 week. On the last day, 24 hour urine was collected and assayed for NH₄⁺ excretion. The animals were sacrificed, kidneys were removed, weighed and cortex was isolated. The protein abundance of ammoniagenic enzymes (glutaminase or GA and glutamate dehydrogenase or GDH) and glutamine transporter SN1 in the cortex was examined by immunoblotting.

Results

The results showed that NH₄⁺ excretion and kidney mass (kidney weight/BW) were significantly increased in DM, KD and HP diet vs. control with a further increase in DM+KD and DM+HP diet vs. DM alone. Immunoblotting studies showed a significant increase in the protein abundance of GA , GDH and SN1 in KD and in HP diet, respectively, vs. control. Interestingly, the protein abundance of GA, GDH and SN1 was unchanged in DM vs. control. The results further showed a significant upregulation of GA (4-fold), GDH (2.5-fold) and SN1 (8-fold) in DM+KD vs. DM alone. In DM+HP group, GA (138%) and GDH (158%) were upregulated, but SN1 remained unchanged vs. DM alone.

Conclusion

1- In all three conditions (DM, KD and HP diet), the stimulation of ammoniagenesis correlates with the development of renal hypertrophy. 2- Diabetic animals exhibited a further increase (additive effect) in ammonia production and renal mass when subjected to potassium depletion or high protein diet, indicating that these conditions activate different and synergistic signaling mechanism(s). 3- KD and HP diet are risk factors for rapid progression of kidney disease in diabetes mellitus.

Funding

• NIDDK Support