Open Access

High glucose activates the alternative ACE2/Ang‑(1‑7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β‑cells

  • Authors:
    • Carmen Härdtner
    • Caroline Mörke
    • Reinhard Walther
    • Carmen Wolke
    • Uwe Lendeckel
  • View Affiliations

  • Published online on: August 14, 2013     https://doi.org/10.3892/ijmm.2013.1469
  • Pages: 795-804
  • Copyright: © Härdtner et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The activation of the classical angiotensin (Ang)‑converting enzyme (ACE)/Ang II/Ang II type 1 receptor (AT1R) axis of the renin‑angiotensin system (RAS) has been associated with islet dysfunction and insulin resistance. Hyperglycaemia, hypertension and obesity, major components of metabolic syndrome, are all associated with increased systemic and tissue levels of Ang II. Whereas it is well established that Ang II, by binding to AT1R, impairs glucose‑stimulated insulin secretion and insulin signaling, the contribution of alternative RAS axes to β‑cell function remains to be fully elucidated. In this study, using the BRIN‑BD11 rat insulinoma cell line, we i) examined the basal expression levels of components of classical and alternative RAS axes and ii) investigated the effects of normal (5.5 mM) and elevated (11, 15, 25 mM) glucose concentrations on their expression and/or enzymatic activity by means of reverse transcription quantitative PCR (RT-qPCR), immunoblot analysis and enzymatic activity assays. The results correlated with the insulin production and release. Essential components of all RAS axes were found to be expressed in the BRIN‑BD11 cells. Components of the alternative RAS axes, ACE2, neutral endopeptidase 24.11, Mas receptor (Mas), aminopeptidases A (APA) and N (APN) and insulin‑regulated aminopeptidase (IRAP) showed an increased expression/activity in response to high glucose. These alterations were paralleled by the glucose‑dependent increase in insulin production and release. By contrast, components of the classical RAS axis, ACE, AT1R and Ang II type 2 receptor (AT2R), remained largely unaffected under these conditions. Glucose induced the activation of the alternative ACE2/Ang‑(1‑7)/Mas and APN/Ang IV/IRAP RAS axes simultaneously with the stimulation of insulin production/release. Our data suggest the existence of a functional link between the local RAS axis and pancreatic β‑cell function; however, further studies are required to confirm this hypothesis.
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October 2013
Volume 32 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Härdtner C, Mörke C, Walther R, Wolke C and Lendeckel U: High glucose activates the alternative ACE2/Ang‑(1‑7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β‑cells. Int J Mol Med 32: 795-804, 2013
APA
Härdtner, C., Mörke, C., Walther, R., Wolke, C., & Lendeckel, U. (2013). High glucose activates the alternative ACE2/Ang‑(1‑7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β‑cells. International Journal of Molecular Medicine, 32, 795-804. https://doi.org/10.3892/ijmm.2013.1469
MLA
Härdtner, C., Mörke, C., Walther, R., Wolke, C., Lendeckel, U."High glucose activates the alternative ACE2/Ang‑(1‑7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β‑cells". International Journal of Molecular Medicine 32.4 (2013): 795-804.
Chicago
Härdtner, C., Mörke, C., Walther, R., Wolke, C., Lendeckel, U."High glucose activates the alternative ACE2/Ang‑(1‑7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β‑cells". International Journal of Molecular Medicine 32, no. 4 (2013): 795-804. https://doi.org/10.3892/ijmm.2013.1469