Exenatide induces an increase in vasodilatory and a decrease in vasoconstrictive mediators

Ajay Chaudhuri; Husam Ghanim; Antoine Makdissi; Kelly Green; Sanaa Abuaysheh; Manav Batra; Nitesh D Kuhadiya; Paresh Dandona

doi:10.1111/dom.12835

Exenatide induces an increase in vasodilatory and a decrease in vasoconstrictive mediators

Diabetes Obes Metab. 2017 May;19(5):729-733. doi: 10.1111/dom.12835. Epub 2017 Feb 22.

Authors

Ajay Chaudhuri¹, Husam Ghanim¹, Antoine Makdissi¹, Kelly Green¹, Sanaa Abuaysheh¹, Manav Batra¹, Nitesh D Kuhadiya¹, Paresh Dandona¹

Affiliation

¹ Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.

PMID: 27891769
DOI: 10.1111/dom.12835

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.

Keywords: blood pressure; exenatide; vasodilatation.

Publication types

Randomized Controlled Trial

MeSH terms

Adenylyl Cyclases / chemistry
Adenylyl Cyclases / genetics
Adenylyl Cyclases / metabolism
Angiotensinogen / antagonists & inhibitors
Angiotensinogen / blood
Anti-Obesity Agents / therapeutic use
Antihypertensive Agents / therapeutic use*
Atrial Natriuretic Factor / agonists*
Atrial Natriuretic Factor / blood
Blood Pressure / drug effects
Cyclic AMP / agonists
Cyclic AMP / blood
Cyclic GMP / agonists
Cyclic GMP / blood
Diabetes Mellitus, Type 2 / blood
Diabetes Mellitus, Type 2 / drug therapy
Diabetes Mellitus, Type 2 / immunology
Diabetes Mellitus, Type 2 / metabolism
Exenatide
Gene Expression Regulation / drug effects*
Glucagon-Like Peptide 1 / agonists*
Glucagon-Like Peptide 1 / metabolism
Humans
Hypoglycemic Agents / therapeutic use
Leukocytes, Mononuclear / drug effects*
Leukocytes, Mononuclear / immunology
Leukocytes, Mononuclear / metabolism
Nerve Tissue Proteins / antagonists & inhibitors*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Obesity / blood
Obesity / drug therapy
Obesity / immunology
Obesity / metabolism
Oncogene Proteins / antagonists & inhibitors*
Oncogene Proteins / genetics
Oncogene Proteins / metabolism
Peptides / therapeutic use*
Renin-Angiotensin System / drug effects
Reproducibility of Results
Single-Blind Method
Transforming Growth Factor beta / antagonists & inhibitors
Transforming Growth Factor beta / blood
Venoms / therapeutic use*

Substances

Anti-Obesity Agents
Antihypertensive Agents
Hypoglycemic Agents
NREP protein, human
Nerve Tissue Proteins
Oncogene Proteins
Peptides
Transforming Growth Factor beta
Venoms
Angiotensinogen
Atrial Natriuretic Factor
Glucagon-Like Peptide 1
Exenatide
Cyclic AMP
Adenylyl Cyclases
Cyclic GMP