Differential effects of angiotensin receptor blockers on pancreatic islet remodelling and glucose homeostasis in diet -induced obese mice

摘要

Obesity leads to adverse endocrine pancreas remodelling, reduced islet lifespan and early type 2 diabetes onset. AT1R blockade shows beneficial pleiotropic effects. This study sought to compare the effects of losartan and telmisartan on pancreatic islets remodelling and glucose homeostasis in diet-induced obese mice. High-fat diet yielded overweight, insulin resistance, islet apoptosis and hypertrophy. Suitable insulin levels and preserved endocrine pancreas structure were correlated to adequate AKT-FOXO1 pathway functioning in losartan-treated animals. Conversely, telmisartan yielded enhanced PDX1 and GLP-1 islet expression along with greater GLP-1 levels, with the consequent better islet glucose sensing and uptake. Greater islet vascularisation coupled with reduced apoptosis and macrophage infiltration seems to underlie the beneficial findings in both treatments. In conclusion, these results provide compelling evidence that two antihypertensive drugs (telmisartan and losartan) ameliorate pancreatic islet structure, glucose handling, and vascularisation in obese mice. Although only telmisartan countered overweight, both drugs yielded reduced apoptosis and islet preservation, with translational potential. (C) 2016 Elsevier Ireland Ltd. All rights reserved.