Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence suggests that the intrarenal renin-angiotensin system (RAS) may play an important role in the development of glomerular changes associated with diabetic nephropathy. In this study, the glomerular RAS was examined in male Sprague-Dawley rats made diabetic with streptozotocin (STZ), and the findings compared with those obtained in control nondiabetic rats. In diabetic rat glomerular extracts, angiotensinogen and angiotensin II (ANG II) levels were increased significantly by 2.2- and 1.9-fold, respectively, compared with nondiabetic controls. No significant differences in ANG I and angiotensin-converting enzyme (ACE) levels were observed between these groups. The HPLC analysis of the glomerular extracts demonstrated that exogenous ANG I was converted into various ANG peptides including ANG II, ANG1-9, and ANG1-7. A significant increase in formation of ANG II from exogenous ANG I was observed in STZ rats compared with control rats. Preincubation of glomerular extracts with captopril resulted in a 20-30% decrease in ANG II conversion from exogenous ANG I in diabetic and control rats. The possible role of ANG1-9 in formation of ANG II was examined by HPLC. Exogenous ANG1-9 in glomerular extracts was converted into ANG II, this conversion being significantly higher in STZ rats than in control rats. These findings provide new information that ANG1-9 is produced in rat glomerular extracts, can be converted to ANG II, and that this conversion is also stimulated in diabetic rat glomeruli. Thus this study demonstrates that in diabetic rats, glomerular ANG II levels are increased due to an increase in angiotensinogen and an increase in the formation of ANG II.
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PMID:A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli. 1570 18

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in developed countries where type 2 diabetes mellitus has reached epidemic proportions. Although the exact pathogenesis of DN is not fully understood and is likely diverse in nature, there are convincing data that the renin-angiotensin system (RAS) is a major mediator of renal injury. Angiotensin II (Ang II), traditionally playing a central role as a mediator of glomerular hemodynamic adaptation and injury, is now recognized to exert proinflammatory action leading to upregulation of chemokines, adhesion molecules, and other fibrogenic growth factors that culminate in a decline of renal function. Hyperglycemia and mechanical stress deriving from glomerular hypertension are the key factors underlying pathogenesis of DN. The common signaling pathways stimulated by high glucose and mechanical insult may act synergistically, thereby accelerating the cell damage. Podocytes are subjected not only to the load of filtered glucose but also to diverse mechanical forces. Both high glucose and mechanical stress may impair the protein systems anchoring the podocyte foot processes in the glomerular basement membrane, therefore blunting resistance of these cells to mechanical forces in addition to the inflammatory insults. Loss of the podocytes is irreversible due to their inability to proliferate and to replenish damaged cells. Podocytes are injured early in the course of DN, which, most likely, underlies further glomerular and renal damage in diabetes. Under normal physiological conditions, podocytes play a specific role in the maintenance of intraglomerular RAS balance with enzymatic activities that predominantly lead to ANG1-7 and ANG1-9 formation, as well as Ang II degradation. ANG1-7 counteracts the proinflammatory actions of Ang II. These enzymatic activities are altered in a nonphysiological environment such as hyperglycemia that mimics diabetic kidney disease. An understanding of the local intraglomerular RAS will provide a novel approach for early stages of DN.
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PMID:The renin-angiotensin system. 2165 66