Study of interaction between nitric oxide and ACE activity in STZ-induced diabetic rats: role of insulin

Sharifi, Azam

doi:10.1016/s1043-6618(04)00097-0

Cited by 4 publications

(7 citation statements)

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“…42,43 There is evidence of a higher activity of this enzyme in serum and some tissues such as ventricle and lung 11,12,16 in STZ-induced diabetic rats, but also a reduction of activity has been described in renal tissue. 18 The objective of this study was to study the association of somatic and nACE protein expression and enzymatic activity in the renal tissue homogenate of Wistar rats, in which DM was induced by streptozotocin. We also aimed to analyse ACE activity in urine and quantify the Ang levels in tissues in the same model in association with DM.…”

Section: Discussionmentioning

confidence: 99%

“…20 mL of solvent was added to 1 g tissue followed by centrifugation at 15,000 rpm for 20 minutes. The samples were concentrated in C 18 Sep-Pak columns activated with methanol (5 mL), tetrahydrofuran (5 mL), hexane (5 mL), methanol (5 mL) and water (10 mL). The peptides were eluted with ethanol, acetic acid and water (90:4:6).…”

Section: Angiotensin Quantification By Hplcmentioning

confidence: 99%

“…[6][7][8] Furthermore, it has been postulated that in diabetes there is a role for the RAS in mediating many of the functional effects such as changes in intraglomerular haemodynamics 9 as well as structural changes in the diabetic kidney at both glomerular and tubulointerstitium levels. 9,10 There is strong evidence that angiotensinconverting enzyme (ACE) activity is increased in serum 5,[11][12][13][14][15] and tissues such as lung, 11,12 ventricle, 16 mesenteric artery, 17 aorta and heart 18 of STZinduced diabetic rats. Insulin treatment could reverse some of these changes, 19 but the mechanism by which insulin treatment affects ACE activity is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Ronchi

Irigoyen

Casarini

2007

J Renin Angiotensin Aldosterone Syst

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Diabetes mellitus (DM) is characterised by alterations in the intrarenal renin-angiotensin system (RAS). Insulin treatment may reverse these changes by an unknown mechanism.We aimed to verify the association between somatic ACE with 136 kDa (sACE) and N-domain ACE with 69 kDa (nACE) from Wistar (W) rat tissue with DM.Three groups were studied: control (CT), insulin treated diabetic (DT) and untreated (D). ACE activity was determined using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates. In D group, urine ACE activity increased for both substrates when compared with CT and DT, despite the decreased activity of renal tissues. Immunostaining of renal tissue demonstrated that ACE is more strongly expressed in the proximaltubule of D than in the same nephron portion in the other groups.Angiotensin (Ang) 1-7 and Ang II are less expressed in DT group when compared with CT and D. Ang II levels decreased in the D and DT groups showed when compared to the control. Ang 1-7 was detected in all studied groups with low levels in DT.The modulation of angiotensin peptides suggests that sACE, nACE,ACE 2 and NEP could have important functions in renal RAS regulation through a counter-regulatory mechanism to protect the kidney in diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Section: Angiotensin Quantification By Hplcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Ronchi

Irigoyen

Casarini

2007

J Renin Angiotensin Aldosterone Syst

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“…Another potential mechanism is blockade of the renin-angiotensin system through inhibition of angiotensin-converting enzyme, which has been shown clinically to increase insulin sensitivity (Henriksen and Jacob, 2003;Damas et al, 2004;Jandeleit-Dahm et al, 2005). In addition to its stimulatory effects on NO synthase, insulin also decreases angiotensin-converting enzyme activity, including activity in the lung (Krulewitz et al, 1984;Erman et al, 1998;Sharifi et al, 2004), thus increasing kinin levels and decreasing angiotensin II. Binding of bradykinin to the B 2 receptor directly increases NO levels, enhances insulin signaling (via insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity), increases GLUT-4 glucose transporter translocation in skeletal muscle, and has been shown to be a potent insulin-dependent enhancer of glucose uptake in muscle and fat (Henriksen and Jacob, 2003;Damas et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Inhalation of Human Insulin Is Associated with Improved Insulin Action Compared with Subcutaneous Injection and Endogenous Secretion in Dogs

Edgerton

Stettler²,

Neal³

et al. 2006

J Pharmacol Exp Ther

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This study compared the effects of endogenous (portal) insulin secretion versus peripheral insulin administration with subcutaneous or inhaled human insulin [INH; Exubera, insulin human (rDNA origin) inhalation powder] on glucose disposal in fasted dogs. In the control group, glucose was infused into the portal vein (Endo; n ϭ 6). In two other groups, glucose was infused portally, whereas insulin was administered peripherally by inhalation (n ϭ 13) or s.c. injection (n ϭ 6) with somatostatin and basal glucagon. In the Endo group, over the first 3 h, the arterial insulin concentration was twice that of the peripheral groups, whereas hepatic sinusoidal insulin levels were half as much.Although net hepatic glucose uptake was greatest in the Endo group, the peripheral groups demonstrated larger increases in nonhepatic glucose uptake so that total glucose disposal was greater in the latter groups. Compared with s.c. insulin action, glucose excursions were smaller and shorter, and insulin action was at least twice as great after INH. Thus, at the glucose dose and insulin levels chosen, peripheral insulin delivery was associated with greater whole-body glucose disposal than endogenous (portal) insulin secretion. INH administration resulted in increased insulin sensitivity in nonhepatic but not in hepatic tissues compared with s.c. delivery.Most patients with diabetes requiring insulin treatment rely on daily injections of insulin. Various alternatives to injectable insulin have been investigated, including insulin patches, pumps, oral formulations, and inhalation. Inhaled human insulin [INH; Exubera, insulin human (rDNA origin) inhalation powder] seems to be a promising alternative for effective, noninvasive insulin delivery to injection. It is approved in the United States and European Union for treatment of hyperglycemia in adults with diabetes mellitus.Insulin delivered by inhalation or s.c. administration enters directly into the peripheral circulation, exposing muscle, fat, and other nonhepatic tissues to relatively higher insulin concentrations than the liver (Cherrington et al., 2004). On the other hand, endogenously secreted insulin enters into the portal vein, exposing the liver to the highest concentrations of insulin. Because insulin has discrete effects on hepatic and nonhepatic tissues, it is important to understand how differences in the route of insulin appearance may affect glucose metabolism, both at the liver and other tissues. Therefore, one purpose of this study was to compare the effect of portal (endogenous) insulin delivery to the effect of insulin delivered peripherally (by inhalation or s.c. injection) on hepatic and nonhepatic glucose metabolism during a simulated oral glucose load.In addition, in clinical trials comparing INH with s.c. insulin (Humulin) delivered, INH reduced the postprandial glucose rise (0 -3 h) at least as effectively as Humulin, with less late (4 -5 h) glucose reduction below baseline (Skyler et al., 2005). Remarkably, compared with s.c. administration, insulin in...

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“…Possible mechanisms of increased nonHGU associated with insulin inhalation have been postulated, including a nitric oxide (NO)-mediated event (Edgerton et al, 2006a) and the blockade of the renin-angiotensin system through inhibition of ACE, which has been shown clinically to increase insulin sensitivity (Henriksen and Jacob, 2003a,b;Damas et al, 2004;Jandeleit-Dahm et al, 2005). In fact, in addition to its stimulatory effects on NO synthase, insulin decreases ACE activity, including activity in the lung (Krulewitz et al, 1984;Erman et al, 1998;Sharifi et al, 2004), thus increasing kinin levels and decreasing ATII. Binding of BK to the B 2 receptor directly increases NO levels, enhances insulin signaling (via insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity), increases glucose transporter-4 glucose transporter translocation in skeletal muscle, and has been shown to be a potent insulin-dependent enhancer of glucose uptake in muscle and fat (Henriksen and Jacob, 2003a;Damas et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Inhaled Insulin Is Associated with Prolonged Enhancement of Glucose Disposal in Muscle and Liver in the Canine

Edgerton

Cherrington²,

Neal³

et al. 2008

J Pharmacol Exp Ther

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Study of interaction between nitric oxide and ACE activity in STZ-induced diabetic rats: role of insulin

Cited by 4 publications

References 0 publications

Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus

Inhalation of Human Insulin Is Associated with Improved Insulin Action Compared with Subcutaneous Injection and Endogenous Secretion in Dogs

Inhaled Insulin Is Associated with Prolonged Enhancement of Glucose Disposal in Muscle and Liver in the Canine

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