1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects
Background: Elevated sympathetic tone stimulates a POS/PI leucocyte phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2D. BQR, a sympatholytic dopamine agonist for treatment of T2DM, improves postprandial dysglycemia and reduces CVD events. Aim: To exam...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2020-06, Vol.69 (Supplement_1) |
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| creator | EZROKHI, MICHAEL CINCOTTA, ANTHONY CERSOSIMO, EUGENIO ADAMS, JOHN M. ALATRACH, MARIAM AGYIN, CHRISTINA TRIPLITT, CURTIS L. COMINOS, NICHOLAS DEFRONZO, RALPH A. |
| description | Background: Elevated sympathetic tone stimulates a POS/PI leucocyte phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2D. 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 phenotype of blood monocytes 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. Blood monocytes were isolated and expression (PCR) of the following genes was quantitated: (i) master antioxidant gene regulators that increase in response to systemic oxidative stress (OS) (oxidation resistance gene 1 [OXR1] and nuclear factor erythroid 2 like 2 [NRF2]); (ii) genes known to induce a proinflammatory profile in T2DM (toll like receptor 2 [TLR2], nuclear factor kappa B p65 [NFkBp65], and L-selectin, a surface adhesion protein that stimulates transendothelial migration and PI biochemistry); (iii) glucocorticoid receptor [GCR] that produces a PI environment.
Results: BQR significantly improved HbA1c (-0.6%; baseline HbA1c=8.3%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). BQR reduced OS response gene transcript levels of OXR1 and NRF2 by 30% (P |
| doi_str_mv | 10.2337/db20-1070-P |
| format | Article |
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Aim: To examine the effect of BQR on POS/PI phenotype of blood monocytes 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. Blood monocytes were isolated and expression (PCR) of the following genes was quantitated: (i) master antioxidant gene regulators that increase in response to systemic oxidative stress (OS) (oxidation resistance gene 1 [OXR1] and nuclear factor erythroid 2 like 2 [NRF2]); (ii) genes known to induce a proinflammatory profile in T2DM (toll like receptor 2 [TLR2], nuclear factor kappa B p65 [NFkBp65], and L-selectin, a surface adhesion protein that stimulates transendothelial migration and PI biochemistry); (iii) glucocorticoid receptor [GCR] that produces a PI environment.
Results: BQR significantly improved HbA1c (-0.6%; baseline HbA1c=8.3%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). BQR reduced OS response gene transcript levels of OXR1 and NRF2 by 30% (P<0.03) and of PI genes TLR2, NFkBp65, GCR, and L-selectin by 40, 33, 26, and 32% respectively (P<0.05). Plasma levels of OS markers (TBARS and nitrotyrosine) and PI cytokines (MCP1 and IL-18) also were significantly reduced (p<0.01-0.05) by BQR.
Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and improves multiple aspects of the POS/PI state in T2DM, providing a potential mechanism for BQR’s cardiovascular protective effect.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db20-1070-P</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Antioxidants ; Bromocriptine ; Cardiovascular diseases ; Diabetes ; Dopamine ; Genes ; Genotype & phenotype ; Glucocorticoids ; Hyperemia ; Hyperglycemia ; Inflammation ; Interleukin 18 ; L-selectin ; Leukocyte migration ; Monocytes ; Nitrotyrosine ; Occlusion ; Oxidative stress ; Phenotypes ; Plasma levels ; Sympathetic nervous system ; TLR2 protein ; Toll-like receptors ; Transcription</subject><ispartof>Diabetes (New York, N.Y.), 2020-06, Vol.69 (Supplement_1)</ispartof><rights>Copyright American Diabetes Association Jun 1, 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>EZROKHI, MICHAEL</creatorcontrib><creatorcontrib>CINCOTTA, ANTHONY</creatorcontrib><creatorcontrib>CERSOSIMO, EUGENIO</creatorcontrib><creatorcontrib>ADAMS, JOHN M.</creatorcontrib><creatorcontrib>ALATRACH, MARIAM</creatorcontrib><creatorcontrib>AGYIN, CHRISTINA</creatorcontrib><creatorcontrib>TRIPLITT, CURTIS L.</creatorcontrib><creatorcontrib>COMINOS, NICHOLAS</creatorcontrib><creatorcontrib>DEFRONZO, RALPH A.</creatorcontrib><title>1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects</title><title>Diabetes (New York, N.Y.)</title><description>Background: Elevated sympathetic tone stimulates a POS/PI leucocyte phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2D. 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 phenotype of blood monocytes 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. Blood monocytes were isolated and expression (PCR) of the following genes was quantitated: (i) master antioxidant gene regulators that increase in response to systemic oxidative stress (OS) (oxidation resistance gene 1 [OXR1] and nuclear factor erythroid 2 like 2 [NRF2]); (ii) genes known to induce a proinflammatory profile in T2DM (toll like receptor 2 [TLR2], nuclear factor kappa B p65 [NFkBp65], and L-selectin, a surface adhesion protein that stimulates transendothelial migration and PI biochemistry); (iii) glucocorticoid receptor [GCR] that produces a PI environment.
Results: BQR significantly improved HbA1c (-0.6%; baseline HbA1c=8.3%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). BQR reduced OS response gene transcript levels of OXR1 and NRF2 by 30% (P<0.03) and of PI genes TLR2, NFkBp65, GCR, and L-selectin by 40, 33, 26, and 32% respectively (P<0.05). Plasma levels of OS markers (TBARS and nitrotyrosine) and PI cytokines (MCP1 and IL-18) also were significantly reduced (p<0.01-0.05) by BQR.
Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and improves multiple aspects of the POS/PI state in T2DM, providing a potential mechanism for BQR’s cardiovascular protective effect.</description><subject>Antioxidants</subject><subject>Bromocriptine</subject><subject>Cardiovascular diseases</subject><subject>Diabetes</subject><subject>Dopamine</subject><subject>Genes</subject><subject>Genotype & phenotype</subject><subject>Glucocorticoids</subject><subject>Hyperemia</subject><subject>Hyperglycemia</subject><subject>Inflammation</subject><subject>Interleukin 18</subject><subject>L-selectin</subject><subject>Leukocyte migration</subject><subject>Monocytes</subject><subject>Nitrotyrosine</subject><subject>Occlusion</subject><subject>Oxidative stress</subject><subject>Phenotypes</subject><subject>Plasma levels</subject><subject>Sympathetic nervous system</subject><subject>TLR2 protein</subject><subject>Toll-like receptors</subject><subject>Transcription</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNotkMtKw0AUhgdRsFZXvsCAmxYZO5dcGne23gotTS8Ld2EyOYMpSabOTMW8hY9sSuUsfjh8_D98CN0y-sCFiEdFzilhNKYkPUM9loiECB5_nKMepYwTFifxJbpybkcpjbrrod8T_Ygn1tRG2XLvywbIao0Hk9V6iJ9qqEpjpQeHJU6tIeanLKQvvwFvvAXnRt2zbHQl61p6Y1s8SJebUTob4oVpjGo94PQTGuPbPeCywakxtmrx1DTemqqCAm_58wJvDvkOlHfX6ELLysHNf_bR9vVlO30n8-XbbPo0JyoKApIo4NE4Z0XExgKiXBRChzrkjOdBLpWmUChFmSrCMI-5iHSQJLqQFBinTHMq-ujuVLu35usAzmc7c7BNt5jxgCVByMY86Kj7E6Wscc6Czva2rKVtM0azo_HsaDw7OsxS8QfRuHNc</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>EZROKHI, MICHAEL</creator><creator>CINCOTTA, ANTHONY</creator><creator>CERSOSIMO, EUGENIO</creator><creator>ADAMS, JOHN M.</creator><creator>ALATRACH, MARIAM</creator><creator>AGYIN, CHRISTINA</creator><creator>TRIPLITT, CURTIS L.</creator><creator>COMINOS, NICHOLAS</creator><creator>DEFRONZO, RALPH A.</creator><general>American Diabetes Association</general><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20200601</creationdate><title>1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects</title><author>EZROKHI, MICHAEL ; CINCOTTA, ANTHONY ; CERSOSIMO, EUGENIO ; ADAMS, JOHN M. ; ALATRACH, MARIAM ; AGYIN, CHRISTINA ; TRIPLITT, CURTIS L. ; COMINOS, NICHOLAS ; DEFRONZO, RALPH A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c644-9ce268b1d6183e6b3d3f5f5212b4bacf0edcc01cd55b7236f499fda0e1201f203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antioxidants</topic><topic>Bromocriptine</topic><topic>Cardiovascular diseases</topic><topic>Diabetes</topic><topic>Dopamine</topic><topic>Genes</topic><topic>Genotype & phenotype</topic><topic>Glucocorticoids</topic><topic>Hyperemia</topic><topic>Hyperglycemia</topic><topic>Inflammation</topic><topic>Interleukin 18</topic><topic>L-selectin</topic><topic>Leukocyte migration</topic><topic>Monocytes</topic><topic>Nitrotyrosine</topic><topic>Occlusion</topic><topic>Oxidative stress</topic><topic>Phenotypes</topic><topic>Plasma levels</topic><topic>Sympathetic nervous system</topic><topic>TLR2 protein</topic><topic>Toll-like receptors</topic><topic>Transcription</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EZROKHI, MICHAEL</creatorcontrib><creatorcontrib>CINCOTTA, ANTHONY</creatorcontrib><creatorcontrib>CERSOSIMO, EUGENIO</creatorcontrib><creatorcontrib>ADAMS, JOHN M.</creatorcontrib><creatorcontrib>ALATRACH, MARIAM</creatorcontrib><creatorcontrib>AGYIN, CHRISTINA</creatorcontrib><creatorcontrib>TRIPLITT, CURTIS L.</creatorcontrib><creatorcontrib>COMINOS, NICHOLAS</creatorcontrib><creatorcontrib>DEFRONZO, RALPH A.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EZROKHI, MICHAEL</au><au>CINCOTTA, ANTHONY</au><au>CERSOSIMO, EUGENIO</au><au>ADAMS, JOHN M.</au><au>ALATRACH, MARIAM</au><au>AGYIN, CHRISTINA</au><au>TRIPLITT, CURTIS L.</au><au>COMINOS, NICHOLAS</au><au>DEFRONZO, RALPH A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2020-06-01</date><risdate>2020</risdate><volume>69</volume><issue>Supplement_1</issue><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Background: Elevated sympathetic tone stimulates a POS/PI leucocyte phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2D. 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 phenotype of blood monocytes 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. Blood monocytes were isolated and expression (PCR) of the following genes was quantitated: (i) master antioxidant gene regulators that increase in response to systemic oxidative stress (OS) (oxidation resistance gene 1 [OXR1] and nuclear factor erythroid 2 like 2 [NRF2]); (ii) genes known to induce a proinflammatory profile in T2DM (toll like receptor 2 [TLR2], nuclear factor kappa B p65 [NFkBp65], and L-selectin, a surface adhesion protein that stimulates transendothelial migration and PI biochemistry); (iii) glucocorticoid receptor [GCR] that produces a PI environment.
Results: BQR significantly improved HbA1c (-0.6%; baseline HbA1c=8.3%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). BQR reduced OS response gene transcript levels of OXR1 and NRF2 by 30% (P<0.03) and of PI genes TLR2, NFkBp65, GCR, and L-selectin by 40, 33, 26, and 32% respectively (P<0.05). Plasma levels of OS markers (TBARS and nitrotyrosine) and PI cytokines (MCP1 and IL-18) also were significantly reduced (p<0.01-0.05) by BQR.
Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and improves multiple aspects of the POS/PI state in T2DM, providing a potential mechanism for BQR’s cardiovascular protective effect.</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db20-1070-P</doi></addata></record> |
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| subjects | Antioxidants Bromocriptine Cardiovascular diseases Diabetes Dopamine Genes Genotype & phenotype Glucocorticoids Hyperemia Hyperglycemia Inflammation Interleukin 18 L-selectin Leukocyte migration Monocytes Nitrotyrosine Occlusion Oxidative stress Phenotypes Plasma levels Sympathetic nervous system TLR2 protein Toll-like receptors Transcription |
| title | 1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects |
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