title: Exenatide induces an increase in vasodilatory and a decrease in vasoconstrictive mediators.
abstract: In view of the known vasodilatory effects of glucagon-like peptide-1 and exenatide, we investigated the effects of exenatide on vasoactive factors. We analysed blood samples and mononuclear cells (MNCs) from a previous study, collected after a single dose and 12 weeks of exenatide or placebo treatment in a series of 24 patients with type 2 diabetes mellitus. After exenatide treatment, plasma concentrations of atrial natriuretic peptide, cyclic guanyl monophosphate (cGMP) and cyclic adenyl monophosphate increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNCs increased significantly after a single dose. Angiotensinogen concentration fell significantly 2 hours after a single dose and at 12 weeks, while renin and angiotensin II levels fell significantly only after a single dose and not after 12 weeks of treatment. Exenatide also suppressed the plasma concentration of transforming growth factor-β and the expression of P311 in MNCs at 12 weeks. Thus, exenatide induces an increase in a series of vasodilators, while suppressing the renin-angiotensin system. These changes may contribute to the overall vasodilatory effect of exenatide.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Ajay
authors.initials: A
authors.lastname: Chaudhuri
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Antoine
authors.initials: A
authors.lastname: Makdissi
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Kelly
authors.initials: K
authors.lastname: Green
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Abuaysheh
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Manav
authors.initials: M
authors.lastname: Batra
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Nitesh
authors.initials: N
authors.lastname: D Kuhadiya
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000808:Angiotensinogen / Q000037:antagonists & inhibitors / Q000097:blood; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000819:agonists* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000819:agonists / Q000097:blood; D006152:Cyclic GMP / Q000819:agonists / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000077270:Exenatide; D005786:Gene Expression Regulation / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015203:Reproducibility of Results; D016037:Single-Blind Method; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000097:blood; D014688:Venoms / Q000627:therapeutic use*
chemical_list: D019440:Anti-Obesity Agents; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; C428027:NREP protein, human; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D010455:Peptides; D016212:Transforming Growth Factor beta; D014688:Venoms; D000808:Angiotensinogen; D009320:Atrial Natriuretic Factor; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006152:Cyclic GMP
keywords: blood pressure; exenatide; vasodilatation