Daily exercise training protects against albuminuria and angiotensin converting enzyme 2 shedding in db/db diabetic mice.

Abstract

Angiotensin II (Ang II) is involved in induction and progression of renal damage in diabetes. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and has been shown to be renoprotective by degrading Ang II to Ang-(1-7). A disintegrin and metalloproteinase 17 (ADAM17)-mediated shedding of renal ACE2 contribute to diabetic nephropathy pathogenesis. Lifestyle modification and metformin are recommended as initial therapies for most patients with type 2 diabetes. The aim of this study was to investigate whether exercise training and/or metformin improve glucose homeostasis and albuminuria and downregulate renal ADAM17 and ACE2 shedding in db/db mice. Seven-week-old normal and db/db mice were subjected either to a sedentary existence or exercise training with and without metformin (150 mg/kg per day) for 10 weeks. Exercise training significantly lowered blood glucose, urinary albumin and ACE2 excretion in db/db mice. ADAM17 and ACE2 proteins were co-localized in cortical tubules of the kidney, indicating a possible interaction. Metformin treatment was effective in lowering hyperglycemia only during the first 2 weeks of treatment. Increased renal ADAM17 in 17-week-old db/db mice was corrected by physical exercise but not metformin. In addition, exercise training reduced plasma triglycerides and enhanced insulin levels of db/db mice. In conclusion, exercise training alone and in combination with metformin prevented shedding of renal ACE2 by decreasing ADAM17 protein. Urinary ACE2 could serve as a prognostic tool for the progression of kidney damage and its attenuation by exercise may partially contribute to its renal protection.

• Authors: Hari K Somineni, Gregory P Boivin, Khalid M Elased
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 221 Issue 2 Pg. 235-51 (May 2014) ISSN: 1479-6805 [Electronic] England
• PMID: 24756098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• Receptors, Leptin
• leptin receptor, mouse
• Metformin
• Peptidyl-Dipeptidase A
• Ace2 protein, mouse
• Angiotensin-Converting Enzyme 2

Topics

• Albuminuria (metabolism, prevention & control)
• Angiotensin-Converting Enzyme 2
• Animals
• Combined Modality Therapy
• Diabetes Complications (prevention & control, urine)
• Diabetes Mellitus, Experimental (complications, genetics, therapy, urine)
• Diabetes Mellitus, Type 2 (complications, therapy, urine)
• Exercise Therapy (methods)
• Hypoglycemic Agents (therapeutic use)
• Kidney (metabolism)
• Male
• Metformin (therapeutic use)
• Mice
• Mice, Transgenic
• Peptidyl-Dipeptidase A (urine)
• Physical Conditioning, Animal (physiology)
• Protein Transport
• Receptors, Leptin (genetics)