Podocytes have also been shown to express angiotensin-converting enzyme 2 (ACE2), which can decrease angiotensin II levels by generation of angiotensin-(1-7).Nadarajah et al. now show that increased podocyte ACE2 activity can attenuate the development of diabetic nephropathy.
Although the renin-angiotensin system has been implicated in the pathogenesis of diabetic nephropathy, angiotensin I-converting enzyme inhibitors have a beneficial effect on diabetic nephropathy independently of their effects on blood pressure and plasma angiotensin II levels.
This risk could be attributed to the increasing activity of ACE and angiotensin II level in the presence of D allele and decreasing NO production in the presence of T allele accelerating diabetic nephropathy.
The widely studied candidate genes of the renin-angiotensin-aldosterone system, angiotensinogen (AGT), and angiotensin II receptor type 1 (AGTR1), are implicated in the development of diabetic nephropathy (DN).
Genetic variation at the AGT gene influences the risk of nephropathy in T2DM patients but not extent of DN severity, and thus represents a potential DN genetic susceptibility locus worthy of replication.
ACE D (P=0.009) and AGT 235T (P=0.026) alleles were associated with the reduced risk of diabetic nephropathy in nonobese and obese patients, respectively.
Comparison of haplotype frequencies identified the rare AGT haplotype as significantly protective against DN, 3.1% cases versus 5.8% controls; chi(2) = 11.05, Pc = 0.009 by the permutation test.
Angiotensin converting enzyme (ACE) generates angiotensin II from angiotensin I, which plays a critical role in the pathophysiology of diabetic nephropathy.
A total of 102 individuals were screened for the presence of the ACE I/D and AGTM235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy.
Further, we discovered that the genes encoding the angiotensin-converting enzyme, angiotensinogen, and angiotensin II type I receptor have a significant combinational effect on conferring susceptibility to diabetic nephropathy.
Angiotensin II type 1 receptor antagonists (AIIA) are beneficial for the prevention of atherosclerosis and diabetic nephropathy suggesting that angiotensin II (Ang II) promotes the development of these diseases.
To elucidate the role of the renin-angiotensin system (RAS) in diabetic nephropathy, we examined the association between diabetic nephropathy in a large cohort of Japanese type 2 diabetic patients and polymorphisms within the genes that encode angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1).
In fact, it has been shown that angiotensin II is involved in almost every pathophysiological process implicated in the development of diabetic nephropathy (haemodynamic changes, hypertrophy, extracellular matrix accumulation, growth factor/cytokine induction, ROS formation, podocyte damage, proteinuria, interstitial inflammation).
In this study, the changes of VEGF expression was examined in the experimental diabetic nephropathy to determine whether these changes were modified by renoprotective intervention by blockers of angiotensin II receptors.
The impact of polymorphisms in the genes coding for angiotensinogen (M235T), ACE (ID), and angiotensin II type 1 receptor (A(1166)-->C) on decline in GFR and doubling of s-creatinine or development of ESRD in patients with type 1 diabetes and diabetic nephropathy (DN) was tested.
Therefore, we investigated the long-term effect of the angiotensin II subtype-1 (AT1) receptor antagonist losartan (100 mg o.d.) on kidney function in II and DD type 1 diabetic patients with diabetic nephropathy.
The two main treatment strategies for prevention of diabetic nephropathy are improved glycaemic control and blood pressure lowering, particularly using drugs such angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists.