Reduced activity of renal angiotensin-converting enzyme in streptozotocin-induced diabetic rats

Maeda, Shiro; Kikkawa, Ryuichi; Haneda, Masakazu; Togawa, Masaki; Koya, Daisuke; Horide, Naoki; Kajiwara, Nobuyuki; Uzu, Takashi; Shigeta, Yukio

doi:10.1016/0891-6632(91)90081-y

Cited by 14 publications

(13 citation statements)

References 22 publications

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“…This would be in keeping with the streptozotocin-treated rat model of diabetes in which kidney ACE mRNA was also decreased. [17][18][19] Against this possibility, however, is our finding of a lack of changes in cardiac ACE mRNA and ACE protein despite exposure to a hyperglycemic environment similar to that prevailing in the kidney.…”

Section: Animal Characteristicscontrasting

confidence: 43%

“…13 Previous studies using the streptozocin (STZ) model of diabetes revealed decreased renal expression of ACE. [17][18][19] A recent study using this rat diabetic model showed a reduction in ACE 2 as well. 18 These previous studies involved diabetic rats with advanced renal lesions.…”

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confidence: 99%

“…18 These previous studies involved diabetic rats with advanced renal lesions. [17][18][19] The aim of the present study was to characterize the expression of ACE and ACE 2 in kidney from diabetic mice (db/db) before the development of nephropathy. The db/db mouse is a genetic model of type 2 diabetes caused by an inactivating mutation of the leptin receptor gene that results in a shorter intracellular domain of the receptor and a failure to transduce signals.…”

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confidence: 99%

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Increased ACE 2 and Decreased ACE Protein in Renal Tubules From Diabetic Mice

et al. 2004

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Abstract-Unlike the ubiquitous angiotensin-converting enzyme (ACE), the ACE-related carboxypeptidase 2 (ACE 2) is predominantly expressed in the heart, kidney, and testis. ACE 2 degrades angiotensin (Ang) II to Ang (1-7) and Ang I to Ang (1-9). We investigated the expression of ACE and ACE 2 in a rodent model of type 2 diabetes. ACE and ACE 2 were measured in kidney and heart from 8-week-old no diabetic control (db/m) mice and diabetic (db/db) mice, which at this young age have obesity and hyperglycemia without nephropathy. Key Words: angiotensin-converting enzyme Ⅲ renin-angiotensin system Ⅲ diabetic nephropathy Ⅲ obesity Ⅲ mice Ⅲ ACE-related carboxypeptidase 2 A lterations within the renin-angiotensin system (RAS) are considered to be pivotal for the development of diabetic complications, particularly diabetic renal disease and hypertension. 1-4 The angiotensin-converting enzyme (ACE), a key element of RAS, is primarily a membrane-bound protein residing on the surface of epithelial and endothelial cells. 5 Through its 2 catalytic domains, ACE cleaves the inactive precursor angiotensin (Ang) I to Ang II, which induces vasoconstriction, aldosterone release, and acts as growth modulator. [5][6][7] Most tissue beds, including the kidney, express a local RAS that acts independently of the circulating system. [7][8][9] There is also a growing body of evidence that implicates the more recently characterized peptides Ang (1-7) and Ang (3-8) as additional bioactive components of the RAS. 10 -12 Recently, a homologue of ACE, an ACE-related carboxypeptidase (ACE 2), has been identified in humans and rodents. [13][14][15] It contains only a single enzymatic site that is capable of catalyzing Ang I to Ang (1-9). It also degrades Ang II to the vasodilator Ang (1-7) and this may counterbalance the Ang II-forming activity of ACE. 15,16 In contrast to ACE, ACE 2 activity is not inhibited by ACE inhibitors. 13 Previous studies using the streptozocin (STZ) model of diabetes revealed decreased renal expression of ACE. [17][18][19] A recent study using this rat diabetic model showed a reduction in ACE 2 as well. 18 These previous studies involved diabetic rats with advanced renal lesions. [17][18][19] The aim of the present study was to characterize the expression of ACE and ACE 2 in kidney from diabetic mice (db/db) before the development of nephropathy. The db/db mouse is a genetic model of type 2 diabetes caused by an inactivating mutation of the leptin receptor gene that results in a shorter intracellular domain of the receptor and a failure to transduce signals. 20,21 As a result of this mutation, hyperglycemia develops in association with insulin resistance and obesity at Ϸ4 to 7 weeks after birth. 22 The db/db mouse eventually has some, but not all, features of

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Section: Animal Characteristicscontrasting

confidence: 43%

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confidence: 99%

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confidence: 99%

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Increased ACE 2 and Decreased ACE Protein in Renal Tubules From Diabetic Mice

et al. 2004

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“…Although there is evidence showing a positive relationship between the development of hypertension and local tissue ACE activity (28), in the present study diabetes and hypertension in association lowered renal tissue ACE activity, which has already been reported in STZ-diabetic Wistar rats (29), STZ-diabetic SHR (30) and genetic models of diabetes (31). Moreover, higher doses of ramipril in diabetic rats progressively lowered tissue ACE activity even more, as was expected and shown before with other drugs of the same class (32).…”

Section: Discussionmentioning

confidence: 52%

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Souza

Machado

Okamoto

et al. 2008

Braz J Med Biol Res

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Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-β1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg·kg -1 ·day -1 (D0.01, N = 14), 1 mg·kg -1 ·day -1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-β1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ≤ 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-β1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.

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“…Some studies have reported a decreased renal ACE mRNA in diabetes [29, 30], while others have reported an increase in ACE mRNA [31]. The lack of a consistent demonstration of the activation of the intrarenal RAS in diabetes may not yet be clear but likely relates to variables such as species differences, differences in duration of diabetes, the degree to which glucose control is maintained, and the heterogeneous expression of RAS components by cells in the kidney might also play a role.…”

Section: Discussionmentioning

confidence: 99%

Renal ACE and ACE2 Expression in Early Diabetic Rats

Moon

Jeong²,

Lee³

et al. 2008

Nephron Exp Nephrol

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AbstractBackground/Aim: The role of angiotensin-converting enzyme (ACE)-related carboxypeptidase-2 (ACE2) in the regulation of the renin-angiotensin system is not well characterized. This study investigated the changes in the expression of ACE and ACE2 in the kidney in early diabetic rats. Methods: Streptozotocin-induced diabetic rats were examined. The concentrations of angiotensin II in plasma, urine, and renal cortex were measured by radioimmunoassay. The mRNA expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and Mas receptor (MasR) in glomeruli and cortex was assessed using real-time PCR. The glomerular and cortical expression of ACE and ACE2 was assessed by immunohistochemistry. Results: For renal cortical tissue, the angiotensin II level was more intensified in the 8-week diabetic rats. Immunohistochemical experiments showed that ACE was increased, but ACE2 was decreased in the glomeruli of 8-week diabetic rats, while both ACE and ACE2 in the tubules were increased. The AT1R mRNA in the glomeruli was decreased, while the MasR mRNA was increased in 2-week diabetic rats. Conclusion: The combined effects of increased ACE and decreased ACE2 in glomeruli may be associated with the activation of the renin-angiotensin system in early diabetic rats, which is known to increase proteinuria.

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Reduced activity of renal angiotensin-converting enzyme in streptozotocin-induced diabetic rats

Cited by 14 publications

References 22 publications

Increased ACE 2 and Decreased ACE Protein in Renal Tubules From Diabetic Mice

Increased ACE 2 and Decreased ACE Protein in Renal Tubules From Diabetic Mice

Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Renal ACE and ACE2 Expression in Early Diabetic Rats

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