Adrenomedullin improves cardiac function and prevents renal damage in streptozotocin-induced diabetic rats

Adrenomedullin (AM) is a potent vasodilating peptide and is involved in cardiovascular and renal disease. In the present study, we investigated the role of AM in cardiac and renal function in streptozotocin (STZ)-induced diabetic rats. A single tail-vein injection of adenoviral vectors harboring the...

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Published in:American journal of physiology: endocrinology and metabolism 2002-12, Vol.46 (6), p.E1291-E1298
Main Authors: DOBRZYNSKI, Eric, MONTANARI, David, AGATA, Jun, JUHONG ZHU, CHAO, Julie, LEE CHAO
Format: Article
Language:English
Subjects:
Associated diseases and complications
Biological and medical sciences
Biotechnology
Diabetes
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Fundamental and applied biological sciences. Psychology
Gene transfer
Genes
Genetic engineering
Genetic technics
Heart
Kidneys
Medical sciences
Metabolism
Methods. Procedures. Technologies
Peptides
Synthetic digonucleotides and genes. Sequencing
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Summary:Adrenomedullin (AM) is a potent vasodilating peptide and is involved in cardiovascular and renal disease. In the present study, we investigated the role of AM in cardiac and renal function in streptozotocin (STZ)-induced diabetic rats. A single tail-vein injection of adenoviral vectors harboring the human AM gene (Ad.CMV-AM) was administered to the rats 1-wk post-STZ treatment (65 mg/kg iv). Immunoreactive human AM was detected in the plasma and urine of STZ-diabetic rats treated with Ad.CMV-AM. Morphological and chemical examination showed that AM gene delivery significantly reduced glycogen accumulation within the hearts of STZ-diabetic rats. AM gene delivery improved cardiac function compared with STZ-diabetic rats injected with control virus, as observed by decreased left ventricular end-diastolic pressure, increased cardiac output, cardiac index, and heart rate. AM gene transfer significantly increased left ventricular long axis (11.69 plus or minus 0.46 vs. 10.31 plus or minus 0.70 mm, n = 10, P < 0.05) and rate of pressure rise and fall (+6,090.1 plus or minus 597.3 vs. +4,648.5 plus or minus 807.1 mmHg/s), (4,902.6 plus or minus 644.2 vs. 3,915.5 plus or minus 805.8 mmHg/s, n = 11, P < 0.05). AM also significantly attenuated renal glycogen accumulation and tubular damage in STZ-diabetic rats as well as increased urinary cAMP and cGMP levels, along with increased cardiac cAMP and Akt phosphorylation. We also observed that delivery of the AM gene caused an increase in body weight along with phospho-Akt and membrane-bound GLUT4 levels in skeletal muscle. These results suggest that AM plays a protective role in hyperglycemia-induced glycogen accumulation and cardiac and renal dysfunction via Akt signal transduction pathways.
ISSN:0193-1849
1522-1555