Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Angiotensin II causes β-cell dysfunction through endoplasmic reticulum stress induced inflammation (#205)

Stanley MH Chan 1 , Yeh-Siang Lau 2 , Simon Potocnik 1 , Jiming Ye 1 , Owen L Woodman 1 , Terence Herbert 1
  1. RMIT University, Bundoora, VIC, Australia
  2. Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

The metabolic syndrome is associated with an increase in the activation of renin angiotensin system (RAS) and inhibition of RAS reduces the incidence of new onset diabetes 1. Importantly, angiotensin II, independently of its vasoconstrictor action, causes β-cell inflammation and dysfunction and this may be an early step in the development of type-2 diabetes2. We show that angiotensin II exposure causes ER stress, increases mRNA expression of the pro-inflammatory cytokines IL-1β and TNF-α, and β-cell dysfunction in murine islets of Langerhans both in vivo and ex vivo and that all these effects are significantly ameliorated by TUDCA, an inhibitor of ER stress. In addition, we show that angiotensin II also causes ER stress and inflammation in clonal β-cells and provide evidence that these effects are mediated by the activation of the angiotensin II type-1 and IP3 receptors, and that inflammation requires the activation of PERK. In summary, these data reveal that the induction of ER stress is critical for angiotensin II induced β-cell dysfunction and thus provides another important rationale for the use of therapies that promote ER homeostasis in the treatment of type-2 diabetes.


  1. Jandeleit-Dahm, K.A., Tikellis, C., Reid, C.M., Johnston, C.I. & Cooper, M.E. Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. Journal of hypertension 23, 463-473 (2005).
  2. Sauter, N.S., et al. Angiotensin II induces interleukin-1beta-mediated islet inflammation and beta-cell dysfunction independently of vasoconstrictive effects. Diabetes 64, 1273-1283 (2015).