title: Differential effects of angiotensin receptor blockers on pancreatic islet remodelling and glucose homeostasis in diet-induced obese mice.
abstract: 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.
authors: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors: Francielle
authors: F
authors: Graus-Nunes
authors: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors: Thatiany de Souza
authors: TS
authors: Marinho
authors: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors: Sandra
authors: S
authors: Barbosa-da-Silva
authors: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors: Marcia Barbosa
authors: MB
authors: Aguila
authors: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors: Carlos Alberto
authors: CA
authors: Mandarim-de-Lacerda
authors: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil. Electronic address: souzamello.uerj@gmail.com.
authors: Vanessa
authors: V
authors: Souza-Mello
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism / Q000187:drug effects; D059305:Diet, High-Fat; D002149:Energy Intake / Q000187:drug effects; D005215:Fasting / Q000097:blood; D005247:Feeding Behavior / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects*; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D000077333:Telmisartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D019808:Losartan; D000077333:Telmisartan
keywords: Apoptosis; Glucose homeostasis; High-fat diet; Losartan; Pancreatic islet; Telmisartan