Kidney Week

Abstract: PO0962

Phosphorylated Akt (pAkt) and Myostatin: The Yin and Yang of the Control of Muscle Protein Metabolism in Patients with Diabetic Kidney Disease

Session Information

• Diabetic Kidney Disease: Clinical - 1
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Picciotto, Daniela, Department of Internal Medicine, Nephrology Division, Policlinico San Martino, Genova, Italy

Daniela Picciotto,

• Milanesi, Samantha, Department of Internal Medicine, Nephrology Division, Policlinico San Martino, Genova, Italy

Samantha Milanesi,

• Saio, Michela, Department of Internal Medicine, Nephrology Division, Policlinico San Martino, Genova, Italy

Michela Saio,

• Brunori, Giuliano, Ospedale Santa Chiara, Trento, Italy

Giuliano Brunori,

• Venturelli, Chiara, Ospedale Santa Chiara, Trento, Italy

Chiara Venturelli,

• Garibotto, Giacomo, Department of Internal Medicine, Nephrology Division, Policlinico San Martino, Genova, Italy

Giacomo Garibotto,

• Verzola, Daniela, Department of Internal Medicine, Nephrology Division, Policlinico San Martino, Genova, Italy

Daniela Verzola,

Background

Muscle wasting is common in patients with diabetic kidney disease (DKD). Both uremia and diabetes cause inflammation and insulin resistance in skeletal muscle, thus promoting wasting. However, the muscle response in DKD is not known yet. Our aim was to evaluate the intracellular signals controlling protein synthesis and degradation in muscle of patients with DKD. We studied intracellular pAkt (a downward effector of the insulin signal), myostatin (MSTN), p38MAPK, MURF and Atrogin in skeletal muscle of patients with diabetic CKD (DCKD) (n=17, age 69 years±7, eGFR 9 ± 3 ml/min/1.73m²) as compared to non diabetic CKD (NDCKD) (n=32, age 67 years±11, eGFR 7.5 ± 2 ml/min/1.73m²) and controls (C) (n=24, age 67 years±11, eGFR 77 ± 13 ml/min/1.73m²).

Methods

Rectus abdominis muscle biopsies were obtained during the insertion of peritoneal dialysis catheters and during elective surgery for abdominal wall hernias (C). Protein expression (pAkt, MSTN, p38MAPK) was evaluated by immunohistochemistry and western blot, mRNA expression (MSTN, Murf, Atrogin) by rt-PCR.

Results

The expression of pAkt was significantly more downregulated in DCKD as compared to NDCKD and C (P <0.05). MSTN expression was significantly lower in C as compared to DCKD and NDCKD (P<0.05). MSTN mRNA was similary upregulated in DCKD and in NDCKD with respectively a 21- and a 18- fold increase compared to controls. Atrogin and Murf mRNA were both upregulated in DCKD and in NDCKD; in DCKD Murf mRNA presented a 18- and atrogin mRNA a 16- fold increase compared to controls while in NDCKD we found respectively a 12- and a 9- fold increase.

Conclusion

With respect to non DKD, intracellular insulin signaling is particularly blunted in muscle of patients with DKD, while myostatin is similarly overexpressed. In diabetes, the abnormal pAkt levels in conjuction with myostatin overexpression are likely to orchestrate the wasting syndrome.