title: Angiotensin receptor blockade increases pancreatic insulin secretion and decreases glucose intolerance during glucose supplementation in a model of metabolic syndrome.
abstract: Renin-angiotensin system blockade improves glucose intolerance and insulin resistance, which contribute to the development of metabolic syndrome. However, the contribution of impaired insulin secretion to the pathogenesis of metabolic syndrome is not well defined. To assess the contributions of angiotensin receptor type 1 (AT₁) activation and high glucose intake on pancreatic function and their effects on insulin signaling in skeletal muscle and adipose tissue, an oral glucose tolerance test (oGTT) was performed in five groups (n = 10/group) of rats: 1) lean strain-control 2) obese Otsuka Long-Evans Tokushima Fatty (OLETF), 3) OLETF + angiotensin receptor blocker (ARB; 10 mg/kg · d olmesartan for 6 wk; OLETF ARB), 4) OLETF + 5% glucose water (HG) for 6 wk (OLETF HG), and 5) OLETF + HG + ARB (OLETF HG/ARB). The glucose response to the oGTT increased 58% in OLETF compared with lean-strain control, whereas glucose supplementation increased it an additional 26%. Blockade of angiotensin receptor reduced the oGTT response 19% in the ARB-treated groups and increased pancreatic insulin secretion 64 and 113% in OLETF ARB and OLETF HG/ARB, respectively. ARB treatment in OLETF ARB and OLETF HG/ARB did not have an effect on insulin signaling proteins in skeletal muscle; however, it reduced pancreatic AT₁ protein expression 20 and 27%, increased pancreatic glucagon-like peptide-1 (GLP-1) receptor protein expression 41 and 88%, respectively, and increased fasting plasma GLP-1 approximately 2.5-fold in OLETF ARB. The results suggest that improvement of glucose intolerance is independent of an improvement in muscle insulin signaling, but rather by improved glucose-stimulated insulin secretion associated with decreased pancreatic AT₁ activation and increased GLP-1 signaling.
authors.affiliation: School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, California 95343, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Jose A
authors.initials: JA
authors.lastname: Viscarra
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Minas
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Rudy M
authors.initials: RM
authors.lastname: Ortiz
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000378:metabolism / Q000517:prevention & control*; D007328:Insulin / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D011919:Rats, Inbred Strains; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D020738:Leptin; D044140:Receptor, Angiotensin, Type 1; D018027:Receptors, Glucagon; D014280:Triglycerides; D005947:Glucose