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

Jun Neng Roan, Han Ni Cheng, Chao Chung Young, Chi Ju Lee, Ming Long Yeh, Chwan Yau Luo, Yau Sheng Tsai, Chen Fuh Lam

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalJournal of Surgical Research
Volume208
DOIs
Publication statusPublished - 2017 Feb 1

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Glucagon-Like Peptide 1
Wound Healing
Wounds and Injuries
Regeneration
Transforming Growth Factors
Hypoglycemic Agents
Superoxides
Blood Vessels
Vascular Endothelial Growth Factor Receptor-2
exenatide
Nitric Oxide Synthase Type III
Extracellular Matrix Proteins
Matrix Metalloproteinase 2
Dermis
Streptozocin
Matrix Metalloproteinases
Interleukin-6
Anti-Inflammatory Agents
Cell Count
Placebos

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

@article{f014ca7ac452492eb59410f91ad2aafd,
title = "Exendin-4, a glucagon-like peptide-1 analogue, accelerates diabetic wound healing",
abstract = "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.",
author = "Roan, {Jun Neng} and Cheng, {Han Ni} and Young, {Chao Chung} and Lee, {Chi Ju} and Yeh, {Ming Long} and Luo, {Chwan Yau} and Tsai, {Yau Sheng} and Lam, {Chen Fuh}",
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language = "English",
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pages = "93--103",
journal = "Journal of Surgical Research",
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Exendin-4, a glucagon-like peptide-1 analogue, accelerates diabetic wound healing. / Roan, Jun Neng; Cheng, Han Ni; Young, Chao Chung; Lee, Chi Ju; Yeh, Ming Long; Luo, Chwan Yau; Tsai, Yau Sheng; Lam, Chen Fuh.

In: Journal of Surgical Research, Vol. 208, 01.02.2017, p. 93-103.

Research output: Contribution to journalArticle

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

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

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JF - Journal of Surgical Research

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