Protective Effects of Adiponectin from Nephropathy and Atherosclerosis in Type 2 Diabetic Rats: Possible Mechanisms
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- Category: Vol. 80, September 2012
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Protective Effects of Adiponectin from Nephropathy and Atherosclerosis in Type 2 Diabetic Rats: Possible Mechanisms,SANDRA M. YOUNAN, HEBA M. SHAWKY and LEILA A. RASHED
Abstract
Backround: Diabetes mellitus and its associated compli-cations have become a public health problem of considerable magnitude. Renal and vascular complications account for most of the excess morbidity and mortality in patients with diabetes mellitus. Clinical studies have demonstrated low plasma adiponectin level in diabetic cases closely linked to renal and atherosclerotic deterioration. The aim of this study is to investigate the effect of adiponectin on diabetic-induced nephropathy and atherosclerosis and the possible underlying protective mechanisms.
Methods: Six rat groups were assigned: Control, type 2- diabetic, non-diabetic-vehicle, diabetic-vehicle, non-diabetic-adiponectin and diabetic-adiponectin groups. The recombinant adiponectin gene was transfected into rats by a single intrap-eritoneal injection. After corresponding treatments for 8 weeks, body mass index, blood pressure, serum glucose, insulin, triglycerides, creatinine adiponectin and TNF-a, blood urea nitrogen (BUN) and urinary microalbumin were measured. Reactive oxygen species (ROS), endothelial nitric oxide synthetase expression (eNOS) in kidney and aorta, transforming growth factor-ß1 (TGF-ß1) and phosphorylated adenosine monophosphate kinase (pAMPK) in the kidney tissue and VCAM-1 expression in aorta were measured. The renal patho-logic changes were observed by light microcopy.
Results: Diabetes significantly reduced serum adiponectin with concomitant significant increase in serum glucose, insulin, triglycerides, TNF-a and creatinine as well as in blood pres-sure, BUN and microalbuminuria with light microscopic evidence of nephropathy in all diabetic groups compared to the control group. Also ROS generation in aorta and kidney, renal TGF-ß1 and aortic VCAM-1 expressions were signifi-cantly increased in diabetic groups compared to control group with significant decrease in renal pAMPK and aortic and renal eNOS expression (p<0.05). Compared with the diabetic group, the diabetic-adiponectin group showed a significant decrease in serum glucose, insulin, triglycerides, TNF-ß and creatinine as well as in blood pressure, BUN and microalbuminuria with improvement of the renal microscopic pathology. Also adi-ponectin significantly decreased ROS generation in aorta and kidney, renal TGF-ß1 and aortic VCAM-1 expressions in diabetic-adiponectin group compared to the diabetic group with significant increase in renal pAMPK and aortic and renal eNOS expression (p<0.05). These beneficial effects were absent in the diabetic-vehicle group indicating a direct role of adiponectin.
Conclusions: Adiponectin decreased TNF-a and ROS, relieved oxidative stress and up-regulated the expression of eNOS in renal and aortic tissues of diabetic rats. In addition adiponectin stimulated the renal AMPK signal pathway and down-regulated the expression of TGF-ß1 in kidney and VCAM-1 in aorta, suggesting a protective effect of adiponectin from diabetic nephropathy and ather osclerosis.