Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes following myocardial infarction in mice.

Sauvé, M., Ban, K., Momen, M.A., Zhou, Y.Q., Henkelman, R.M., Husain, M., Drucker, D.J.
Journal   Diabetes
Species  
Analytes Measured   GLP-1
Matrix Tested   Plasma
Year   2010
Volume   59
Page Numbers   1063-73
Application   Metabolic
Abstract

OBJECTIVE: Glucagon-like peptide-1 (7-36)amide (GLP-1) is cleaved by dipeptidyl peptidase-4 (DPP-4) to GLP-1 (9-36)amide. We examined whether chemical inhibition or genetic elimination of DPP-4 activity affects cardiovascular function in normoglycemic and diabetic mice after experimental myocardial infarction. RESEARCH DESIGN AND

METHODS: Cardiac structure and function was assessed by hemodynamic monitoring and echocardiography in DPP-4 knockout (Dpp4(-/-)) mice versus wild-type (Dpp4(+/+)) littermate controls and after left anterior descending (LAD) coronary artery ligation-induced myocardial infarction (MI). Effects of sustained DPP-4 inhibition with sitagliptin versus treatment with metformin were ascertained after experimental MI in a high-fat diet-streptozotocin model of murine diabetes. Functional recovery from ischemia-reperfusion (I/R) injury was measured in isolated hearts from Dpp4(-/-) versus Dpp4(+/+) littermates and from normoglycemic wild-type (WT) mice treated with sitagliptin or metformin. Cardioprotective signaling in the murine heart was examined by RT-PCR and Western blot analyses.

RESULTS: Dpp4(-/-) mice exhibited normal indexes of cardiac structure and function. Survival post-MI was modestly improved in normoglycemic Dpp4(-/-) mice. Increased cardiac expression of phosphorylated AKT (pAKT), pGSK3beta, and atrial natriuretic peptide (ANP) was detected in the nonischemic Dpp4(-/-) heart, and HO-1, ANP, and pGSK3beta proteins were induced in nonischemic hearts from diabetic mice treated with sitagliptin or metformin. Sitagliptin and metformin treatment of wild-type diabetic mice reduced mortality after myocardial infarction. Sitagliptin improved functional recovery after I/R injury ex vivo in WT mice with similar protection from I/R injury also manifest in hearts from Dpp4(-/-) versus Dpp4(+/+) mice.

CONCLUSIONS: Genetic disruption or chemical inhibition of DPP-4 does not impair cardiovascular function in the normoglycemic or diabetic mouse heart.

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