DPP-4 Inhibition by Sitagliptin Improves the Myocardial Response to Dobutamine Stress and Mitigates Stunning in a Pilot Study of Patients with Coronary Artery Disease.

Read, P.A., Khan, F.Z., Heck, P.M., Hoole, S.P., Dutka, D.P.
Journal   Circ Cardiovasc Imaging.
Species  
Analytes Measured   GLP-1
Matrix Tested   Plasma
Year   2010
Volume   3
Page Numbers   195-201
Application   Metabolic
Abstract
BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted postprandially that promotes myocardial glucose uptake. The active amide GLP-1 (7-36) is degraded by the enzyme DPP-4, and drugs that inhibit this enzyme (such as sitagliptin) have been introduced to treat type 2 diabetes. We assessed the hypothesis that increasing the plasma concentration of GLP-1 by DPP-4 inhibition would protect the heart from ischemic left ventricular (LV) dysfunction during dobutamine stress echocardiography in patients with coronary artery disease.

METHODS AND RESULTS: Fourteen patients with coronary artery disease and preserved LV function awaiting revascularization were studied. After either a single dose of 100 mg sitagliptin or placebo, 75 g of glucose was given orally to promote GLP-1 secretion and dobutamine stress echocardiography was conducted with tissue Doppler imaging at rest, peak stress, and 30 minutes. After sitagliptin, plasma GLP-1 (7-36) was increased at peak stress (16.5+/-10.7 versus 9.7+/-8.7 pg/mL; P=0.003) and in recovery (12.4+/-5.5 versus 9.0+/-5.5 pg/mL; P=0.01), and the LV response to stress was enhanced (ejection fraction, 72.6+/-7.2 versus 63.9+/-7.9%, P=0.0001; mitral annular systolic velocity, 12.54+/-3.18 versus 11.49+/-2.52 cm/s; P=0.0006). DPP-4 inhibition also improved LV regional function in the 12 paired nonapical segments assessed by peak systolic tissue Doppler (velocity, 10.56+/-4.49 versus 9.81+/-4.26 cm/s, P=0.002; strain, -15.9+/-6.3 versus -14.6+/-6.6%, P=0.01; strain rate, -2.04+/-1.04 versus -1.75+/-0.98 s(-1), P=0.0003). This was predominantly due to a cardioprotective effect on ischemic segments (velocity in ischemic segments, 9.77+/-4.18 versus 8.74+/-3.87, P=0.007; velocity in nonischemic segments, 11.51+/-4.70 versus 11.14+/-4.38, P=0.14). In recovery, sitagliptin attenuated the postischemic stunning seen after the control study.

CONCLUSIONS: The augmentation of GLP-1 (7-36) by inhibition of DPP-4 improves global and regional LV performance in response to stress and mitigates postischemic stunning in humans with coronary artery disease. Clinical Trial Registration- URL: http://www.isrctn.org. Unique identifier: ISRCTN78649100.

View Publications

Related Products

U-PLEX Custom Metabolic Group 1 (hu) Assays
BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Metabolic Group 1 (hu) Assays
BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
U-PLEX Diabetes Combo 1 (hu)
C-Peptide, GIP (total), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) | Human
Multiplex
U-PLEX Human GLP-1 (total) Assay
GLP-1 (total) | Human
Singleplex
U-PLEX Metabolic Combo 1 (hu)
BAFF, BDNF, β-NGF, C-Peptide, FGF-21, FGF-23, FSH, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, Luteinizing Hormone (LH), PP, Proinsulin, PYY (total) | Human
Multiplex
U-PLEX Obesity Combo 2 (hu)
C-Peptide, FGF-23, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) | Human
Multiplex
U-PLEX Human GLP-1 (total) Antibody Set
GLP-1 (total) | Human
GLP-1 (total) Antibody
GLP-1 (total) | Human
V-PLEX GLP-1 Total Kit
GLP-1 (total) | Human, Mouse, Non-human primate, Rat, Canine
Singleplex
V-PLEX Plus GLP-1 Total Kit
GLP-1 (total) | Human, Mouse, Non-human primate, Rat, Canine
Singleplex
GLP-1 (total) Control Pack
GLP-1 (total) | Human, Mouse, Non-human primate, Rat, Canine
R-PLEX Human GLP-1 Total Antibody Set
GLP-1 (total) | Human
Singleplex
Total GLP-1 Antibody
GLP-1 (total)
Total GLP-1 (ver. 2) Kit
GLP-1 (total) | Canine, Human, Non-human primate, Mouse, Rat
Singleplex
Human Active GLP-1(7-36)amide, Insulin, Glucagon, Leptin Kit
GLP-1 (active), Glucagon, Insulin, Leptin | Human
Multiplex
Human Active GLP-1, Insulin, Glucagon, Leptin Kit
GLP-1 (active), Glucagon, Insulin, Leptin | Human
Multiplex
Human GLP-1(7-36)amide, Glucagon, Insulin Kit
GLP-1 (active), Glucagon, Insulin | Human
Multiplex
Mouse/Rat GLP-1 (7-36)amide, Glucagon, Insulin Kit
GLP-1 (total), Glucagon, Insulin | Mouse, Rat
Multiplex
Mouse/Rat Active GLP-1 (7-36)amide, Insulin, Glucagon Kit
GLP-1 (total), Glucagon, Insulin | Mouse, Rat
Multiplex
Mouse/Rat Total Active GLP-1, Insulin, Glucagon Kit
GLP-1 (total), Glucagon, Insulin | Mouse, Rat
Multiplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters