756-P: Bromocriptine-QR (BQR) Ameliorates Immunocyte Pro-Oxidative Stress/Proinflammatory (POS/PI) and ER Stress Phenotype in T2DM Subjects

Background: Both CNS reduced dopaminergic and elevated sympathetic tone converge to stimulate a POS/PI phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2DM. BQR, a sympatholytic dopamine agonist for treatment of T2DM, improves postprandial dysglycemia and reduces CVD events. Aim: To examine the effect of BQR on POS/PI/ER stress phenotype of peripheral blood mononuclear (PBMN) cells in T2DM. Study Design: 15 T2DM subjects treated with a GLP-1 RA received BQR (3.2 mg/day) for 16 weeks. Endothelial function was measured by post-occlusion hyperemia. Postprandial glucose metabolism was assessed by meal tolerance test with the double tracer technique (Endo Diab Metab 2018:e00034). Blood PBMN cells were isolated and expression of genes (RT-qPCR) from the following cell physiologic systems was quantitated: (i) multiple-pathway antioxidant regulators that increase in response to systemic oxidative stress (OS); (ii) genes known to be expressed and operative in the ER stress response (including associated autophagy) (see Table for specific gene details). Results: See Table. Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and markedly attenuates the POS/PI/ER stress condition in plasma and PBMN cells of T2DM subjects, providing potential mechanisms for BQR’s CV protective effect. Disclosure M. Ezrokhi: Employee; Self; VeroScience LLC. A. H. Cincotta: Employee; Self; VeroScience LLC, Employee; Spouse/Partner; VeroScience LLC, Stock/Shareholder; Self; VeroScience LLC. E. Cersosimo: None. J. M. Adams: None. M. Alatrach: None. C. Agyin: None. C. L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Xeris Pharmaceuticals, Inc. N. Cominos: Employee; Self; VeroScience LLC. R. A. Defronzo: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk.