Chronic administration of the angiotensin type 2 receptor agonist C21 improves insulin action in C57BL/6 mice

TOBLLI JE; MUÑOZ MC; DIEGO TOMAS QUIROGA; GIL C; DOMINICI FP

Conferencia; Gordon Research Conference Angiotensin; 2018

Angiotensin II exerts a negative modulation of insulin action both in vitro and in vivo. Chronic elevation of Ang II circulating levels lead to insulin resistance through an angiotensin type 1 receptor (AT1R)-mediated mechanism. In contrast, in animal models of both insulin resistance and type 2 diabetes, administration of synthetic angiotensin type 2 receptor (AT2R) agonist C21 has been shown to have a beneficial effect, improving insulin action. This evidence indicates that the AT2R could have a role in the control of insulin action and glucose homeostasis.Folli F et al. Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. J Clin Invest 100: 2158?2169, 1997.Henriksen EJ. Improvement of insulin sensitivity by antagonism of the renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 293: R974?R980, 2007.Favre GA et al. Modulation of glucose metabolism by the renin-angiotensin-aldosterone system. Am J Physiol Endocrinol Metab.308E435-E449, 2015.Shao C et al. Angiotensin type 2 receptor in pancreatic islets of adult rats: a novel insulinotropic mediator. Am J Physiol Endocrinol Metab 305: E1281?1291, 2013.Oshima K, et al. Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation. PLoS One 7(11): e48387, 2012Shum M et al. Angiotensin II type 2 receptor promotes adipocyte differentiation and restores adipocyte size in high-fat/high-fructose diet-induced insulin resistance in rats. Am J Physiol Endocrinol Metab 304: E197?E210, 2013. Nag S et al. Chronic angiotensin AT2R activation prevents high-fat diet-induced adiposity and obesity in female mice independent of estrogen. Metabolism 64: 814?825, 2015. Shao C et al. Activation of angiotensin type 2 receptors partially ameliorates streptozotocin-induced diabetes in male rats by islet protection. Endocrinology 155: 793?804, 2014. Wang L, Wang Y, Li XY, Leung PS. Angiotensin II type 2 receptor activation with compound 21 augments islet function and regeneration in streptozotocin-induced neonatal rats and human pancreatic progenitor cells. Pancreas 46: 395?404, 2017.