Diabetes Metab J.  2011 Jun;35(3):243-247. 10.4093/dmj.2011.35.3.243.

Angiotensin II Inhibits Insulin Binding to Endothelial Cells

• Oh SJ
• Ha WC
• Lee JI
• Sohn TS
• Kim JH
• Lee JM
• Chang SA
• Hong OK
• Son HS

• KMID: 2175427
• DOI: http://doi.org/10.4093/dmj.2011.35.3.243

Abstract

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(-7)M 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 microM, 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.

Keyword

Angiotensin II; Angiotensin II receptor blocker; Endothelium; Insulin resistance; Transcapillary insulin transport

MeSH Terms

Acrylates
Angiotensin II
Angiotensins
Cell Membrane
Cytosol
Endothelial Cells
Endothelium
Glucose
Imidazoles
Insulin
Insulin Resistance
Plasma
Receptor, Insulin
Thiophenes
Vasodilation
Acrylates
Angiotensin II
Angiotensins
Glucose
Imidazoles
Insulin
Receptor, Insulin
Thiophenes

Figure

• 

  Fig. 1 The effect of angiotensin II (ATII) on insulin binding. Bovine aortic endothelial cells were pretreated with 10-7M ATII, then subjected to [125I]-insulin (0.5 µCi/well). Binding assays were performed as described in Methods. aP<0.05; control vs. ATII.

• 

  Fig. 2 The effect of angiotensin receptor blocker (eprosartan) on insulin binding. Bovine aortic endothelial cells were preincubated with eprosartan (0.02, 0.2, 2, 20, and 200 µM) for 30 minutes, and then [125I]-insulin (0.5 µCi/well) and angiotensin II (ATII) (10-7M) were added for 60 minutes. Binding assays were performed as described in Methods. aP<0.05; ATII vs. eprosartan.

• 

  Fig. 3 The changes in the amounts of insulin receptor beta subunit (IRβ) on the plasma membrane and in the cytosol due to treatment with insulin and angiotensin II (ATII). (A) Bovine aortic endothelial cells were treated with 10-7M insulin and 10-7M ATII. (B) Bovine aortic endothelial cells were preincubated with eprosartan (200 µM) for 30 minutes, then 10-7M insulin and 10-7M ATII were added. The amounts of IRβ were measured using Western blotting. Membrane and cytosol proteins were separated and extracted using the MEM-PER mammalian membrane protein extraction kit.

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