The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Attenuates Inflammation and Accelerates Epithelialization in Wounds of Diabetic ob/ob Mice.1

Schürmann C, Linke A, Engelmann-Pilger K, Steinmetz C, Mark M, Pfeilschifter J, Klein T, Frank S.
Journal   J Pharmacol Exp Ther.
Species  
Analytes Measured   GLP-1
Matrix Tested   Wound lysates
Year   2012
Volume   342
Page Numbers   71-80
Application   Metabolic
Abstract
In recent years, new and effective therapeutic agents for blood glucose control have been added to standard diabetes therapies: dipeptidyl peptidase-4 (DPP-4) inhibitors, which prolong the bioavailability of the endogenously secreted incretin hormone glucagon-like peptide-1 (GLP-1). Full-thickness excisional wounding was performed in wild-type (C57BL/6J) and diabetic [C57BL/6J-obese/obese (ob/ob)] mice. DPP-4 activity was inhibited by oral administration of linagliptin during healing. Wound tissue was analyzed by using histological, molecular, and biochemical techniques. In healthy mice, DPP-4 was constitutively expressed in the keratinocytes of nonwounded skin. After skin injury, DPP-4 expression declined and was lowest during the most active phase of tissue reassembly. In contrast, in ob/ob mice, we observed increasing levels of DPP-4 at late time points, when delayed tissue repair still occurs. Oral administration of the DPP-4 inhibitor linagliptin strongly reduced DPP-4 activity, stabilized active GLP-1 in chronic wounds, and improved healing in ob/ob mice. At day 10 postwounding, linagliptin-treated ob/ob mice showed largely epithelialized wounds characterized by the absence of neutrophils. In addition, DPP-4 inhibition reduced the expression of the proinflammatory markers cyclooxygenase-2 and macrophage inflammatory protein-2, but enhanced the formation of myofibroblasts in healing wounds from ob/ob mice. Our data suggest a potentially beneficial role of DPP-4 inhibition in diabetes-affected wound healing.

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