The pro-healing effect of exendin-4 on wounds produced by abrasion in normoglycemic mice

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

“…In excisional wound tissue of diabetic rats, it was shown that activation of GLP1 receptors reduced the formation of superoxide anions, ameliorated wound closure by reducing cytokines and inflammatory cells infiltration [104], and by inducing angiogenic activity through the increased expression of VEGF and HIF1α [105]. Besides stimulation of proliferation and migration of endothelial cells in the wounded area, GLP1 increased also endothelial precursor cells thus facilitating capillary tube formation and neovascularization [104,106]. Finally, GLP1 appears to intervene also in the remodeling phase of the healing process by stimulating TGFβ1 production that, through the increased proliferation of fibroblasts, synthesis of collagen, stimulation of MMP activity, and remodeling of the extracellular matrix, is crucial for the healing event [104].…”

Blue LED light modulates inflammatory infiltrate and improves the healing of superficial wounds

“…One abrasion was irradiated while the other one was left to A semi-quantitative evaluation of inflammatory infiltration on the H&E-stained sections was performed. 5 Cells positive for antigens were counted, and a degranulation index of mast cells was established by using the Image J 1.37v program as previously described. 6 Differences were subjected to variance analysis using StatPlus software.…”

“…After treatment, tissue excision was performed at different points in time(1, 3, 6, 9, 12, 18, and 24 hours), and healthy dorsal skin samples were used as controls. Biopsies were frozen, and sections were analyzed using histological methods and immunofluorescence staining 5. Hematoxylineosin was used to analyze the entire infiltrate, while specific cell types and cytokines were revealed by means of corresponding markers: Avidin (1:400, Sigma) for mast cells; CD31 (1:50, Abcam) for endothelial cells5 ; MHCII (1:50, Abcam) for dendritic cells, TGF-beta(1:50, Abcam) and TNFalfa for their differentiation (1:30, Abcam); CD68 (1:100, Abcam) and CD206 (1:50, Abcam) for M1 and M2 macrophages; CD11c (1:100, Abcam) for myeloid dendritic cells; CD45 for plasmacytoid dendritic cells (1:200, Abcam); and CD25 (1:100, Abcam) for T reg cells.…”

Exendin-4, a glucagon-like peptide-1 analogue, accelerates diabetic wound healing

“…To our knowledge, two previous studies had investigated the applications of Glp-1 analogues or dipeptidyl-peptidase-IV inhibitors (DDP-IV is an aminopeptidase that catalyzes Glp-1) in wound regeneration in normoglycemic or animals with metabolic syndrome. 32,47 Topical injection of high dose Ex4 (5 mg/kg) accelerated wound healing rates through activation of myofibroblasts in nondiabetic mice. 47 Schü rmann et al 32 showed that oral administration of linagliptin (a dipeptidylpeptidase-IV inhibitor, 3 mg/kg/d) in diabetic obese mice enhanced re-epithelialization of excisional wounds at 10 d after surgery by attenuation of infiltration of neutrophils and proinflammatory reaction.…”

“…32,47 Topical injection of high dose Ex4 (5 mg/kg) accelerated wound healing rates through activation of myofibroblasts in nondiabetic mice. 47 Schü rmann et al 32 showed that oral administration of linagliptin (a dipeptidylpeptidase-IV inhibitor, 3 mg/kg/d) in diabetic obese mice enhanced re-epithelialization of excisional wounds at 10 d after surgery by attenuation of infiltration of neutrophils and proinflammatory reaction. In addition to the antiinflammatory and proliferative properties, our study provides more integrated and additional mechanistic investigations into the therapeutic effects of Ex4 in the wound regeneration of diabetes by modulation of regional or systemic inflammation, promotion of angiogenesis, and potentiation of wound maturation.…”