TY - JOUR
T1 - Exendin-4, a glucagon-like peptide-1 analogue, accelerates diabetic wound healing
AU - Roan, Jun Neng
AU - Cheng, Han Ni
AU - Young, Chao Chung
AU - Lee, Chi Ju
AU - Yeh, Ming Long
AU - Luo, Chwan Yau
AU - Tsai, Yau Sheng
AU - Lam, Chen Fuh
N1 - Funding Information:
This work was supported by A Landmark Project to Promote Innovation & Competitiveness of Clinical Trials by the Excellent Clinical Trial and Research Center in National Cheng Kung University Hospital (grant:104-TDU-B-211-113002 and MOHW105-TDU-B-211-133016 to J.-N.R.); the National Cheng Kung University Hospital (grant: NCKUH- 10407002 to J.-N.R.); the National Science Council of Taiwan (grant: MOST 103-2314-B-006-051 to J.-N.R. and MOST 105-2314-B-303-007-MY2 to C.-F.L.); and the Buddhist Tzu Chi General Hosptial (grant: TCRD105-06 to C.-F.L. ).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Background Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. Materials and methods Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0.5 μg/kg/d, i.p.) for 2 wk. The final-to-initial wound area ratio was measured for 14 d. Levels of superoxide anions and proinflammatory cytokines in the wound were determined. Angiogenesis was assessed using the Matrigel assay. Expression levels of proangiogenic factors and extracellular matrix proteins were measured. Results Ex4 restored wound closure in diabetic rats and significantly suppressed the generation of superoxide anions and interleukin-6 in wounds. The number of circulating endothelial progenitor (CD34+/KDR+) cells increased significantly in Ex4-treated diabetic rats, which also showed increased capillary tube formation. Protein levels of vascular endothelial growth factor receptor-2, phosphorylated endothelial nitric oxide synthase, matrix metalloproteinase-2, and transforming growth factor-β were increased in diabetic rats receiving Ex4 therapy. Ex4-enhanced vascularity, dermal regeneration, and epidermal regeneration, while it decreased hemorrhaging and increased the number of proliferative cells in the dermis. Conclusions Ex4 accelerated excisional wound healing in subjects with diabetes. Glp-1R activation attenuates inflammatory response and enhances angiogenesis during the early proliferation phase of wound healing in diabetic subjects, while it enhances transforming growth factor-β/matrix metalloproteinase-mediated regeneration during the maturation phase. These results suggest that Ex4 could be used as a standard hypoglycemic agent in diabetic patients with wound injury.
AB - Background Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. Materials and methods Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0.5 μg/kg/d, i.p.) for 2 wk. The final-to-initial wound area ratio was measured for 14 d. Levels of superoxide anions and proinflammatory cytokines in the wound were determined. Angiogenesis was assessed using the Matrigel assay. Expression levels of proangiogenic factors and extracellular matrix proteins were measured. Results Ex4 restored wound closure in diabetic rats and significantly suppressed the generation of superoxide anions and interleukin-6 in wounds. The number of circulating endothelial progenitor (CD34+/KDR+) cells increased significantly in Ex4-treated diabetic rats, which also showed increased capillary tube formation. Protein levels of vascular endothelial growth factor receptor-2, phosphorylated endothelial nitric oxide synthase, matrix metalloproteinase-2, and transforming growth factor-β were increased in diabetic rats receiving Ex4 therapy. Ex4-enhanced vascularity, dermal regeneration, and epidermal regeneration, while it decreased hemorrhaging and increased the number of proliferative cells in the dermis. Conclusions Ex4 accelerated excisional wound healing in subjects with diabetes. Glp-1R activation attenuates inflammatory response and enhances angiogenesis during the early proliferation phase of wound healing in diabetic subjects, while it enhances transforming growth factor-β/matrix metalloproteinase-mediated regeneration during the maturation phase. These results suggest that Ex4 could be used as a standard hypoglycemic agent in diabetic patients with wound injury.
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U2 - 10.1016/j.jss.2016.09.024
DO - 10.1016/j.jss.2016.09.024
M3 - Article
C2 - 27993221
AN - SCOPUS:84993981986
SN - 0022-4804
VL - 208
SP - 93
EP - 103
JO - Journal of Surgical Research
JF - Journal of Surgical Research
ER -