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2 "Angiotensin II receptor blocker"
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Original Articles
Angiotensin II Inhibits Insulin Binding to Endothelial Cells
Su-Jin Oh, Won-Chul Ha, Jee-In Lee, Tae-Seo Sohn, Ji-Hyun Kim, Jung-Min Lee, Sang-Ah Chang, Oak-Kee Hong, Hyun-Shik Son
Diabetes Metab J. 2011;35(3):243-247.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.243
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  • 27 Download
  • 6 Crossref
AbstractAbstract PDFPubReader   
Background

Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance.

Methods

After treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol.

Results

After treatment of 10-7M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05). ATII receptor blocker (eprosartan) dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05). At 200 µM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol.

Conclusion

ATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.

Citations

Citations to this article as recorded by  
  • Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle
    Dino Premilovac, Emily Attrill, Stephen Rattigan, Stephen M Richards, Jeonga Kim, Michelle A Keske
    Cardiovascular Research.2019; 115(3): 590.     CrossRef
  • Angiotensin II type 2 receptor inhibits expression and function of insulin receptor in rat renal proximal tubule cells
    Yang Yang, Caiyu Chen, Chunjiang Fu, Zaicheng Xu, Cong Lan, Yongchun Zeng, Zhi Chen, Pedro A. Jose, Ye Zhang, Chunyu Zeng
    Journal of the American Society of Hypertension.2018; 12(2): 135.     CrossRef
  • Endothelial function, its relation to arterial hypertension and the possibility of its modulation
    Vladislav Biel, Jan Novák, Luděk Pluháček, Jiří Špác
    Vnitřní lékařství.2018; 64(7-8): 762.     CrossRef
  • Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer’s Disease
    Juan M. Saavedra
    Cellular and Molecular Neurobiology.2016; 36(2): 259.     CrossRef
  • Ameliorative effect of eprosartan on high-fat diet/streptozotocin-induced early diabetic nephropathy in rats
    Mohamed A. Morsy, Gehan H. Heeba, Magda E. Mahmoud
    European Journal of Pharmacology.2015; 750: 90.     CrossRef
  • Metabolic actions of angiotensin II and insulin: A microvascular endothelial balancing act
    Ranganath Muniyappa, Sahzene Yavuz
    Molecular and Cellular Endocrinology.2013; 378(1-2): 59.     CrossRef
Effect of Peroxisome Proliferator Activated Receptor-gamma Agonist, Angiotensin II Receptor Blocker and alpha-lipoic Acid on Renal VEGF Expression in Diabetic Nephropathy.
Jang Hyun Koh, Yeon Lee, Mi Jin Kim, Young Goo Shin, Eun Young Lee, Choon Hee Chung
Korean Diabetes J. 2004;28(5):367-376.   Published online October 1, 2004
  • 1,255 View
  • 34 Download
AbstractAbstract PDF
BACKGROUND
Diabetic nephropathy is one of the most serious complications in diabetes mellitus, and it is the leading cause of end stage renal disease. It has been reported that angiotensin converting enzyme inhibitor (ACEi) reduces the vascular endothelial growth factor (VEGF) expression, and so it plays an important role in reducing the renal damage. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonist is known to reduce insulin resistance in type 2 diabetic patients. In the previous study, PPAR-gamma agonist was shown to lower VEGF expression in the retina, but it increased the plasma VEGF level. Alpha-lipoic acid (alpha-LA), which is an antioxidant, lowers the increased level of VEGF in retina as well. The precise role of PPAR-gamma agonist and alpha-LA on renal VEGF expression in diabetic nephropathy is still uncertain. We studied the effect of PPAR-gamma agonist, angiotensin II receptor blocker (ATIIRB) and alpha-LA on the renal VEGF expression in diabetic rats. METHODS: We used 60 Sprague-Dawley male rats, those were 8 weeks old and weighted about 300 g each as the study subjects. Among them, 48 rats were chosen and injected with streptozotocin (70 mg/kg) into peritoneal cavity to induce diabetes mellitus. The rast were than divided into 5 groups. Group I was a normal control group (n=12), group II was diabetic control group (n=12), group III was diabetic group that was given with PPAR-gamma agonist (n=12), group IV was the diabetic group that was given ATIIRB (n=12), and group V was the diabetic rats that were given alpha-LA (n=12). We measured their body weight, blood glucose levels, 24 hour urine protein and albumin levels at the baseline, the 8th and the 16th weeks of the experiment. On the 16th weeks of our experiment we extracted the kidneys to measure the glomerular volume, the optical density of the VEGF staining and VEGF mRNA expression. RESULTS: At the beginning of the study, the 5 groups all showed similar 24 hour urine albumin levels. At the 8th week, group II showed an increased urine albumin level of 143.4 +/- 117.2 mg/day; this was greater than that of group IV (60.7+/-30.6 mg/day) (p<0.05). The glomerular volume and optical densities of VEGF expression were significantly reduced in group III, IV and V compared to group II. For group IV and V, the renal VEGF mRNA expression was significantly lower than that of group II, but group III showed no significant difference. from group II. CONCLUSION: Angiotensin II receptor blocker delayed the progression of diabetic nephropathy. PPAR-gamma agonist and alpha-lipoic acid did not have any protective effect against the progression of diabetic nephropathy in spite of the decreased VEGF expression noted in this study.

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