Application of low-dose insulin in diabetes refractory wound healing: Epithelialization, collagen deposition and angiogenesis

doi:10.3969/j.issn.2095-4344.2013.20.006

Abstract

Abstract:

BACKGROUND: Diabetes can influence the normal course of wound healing, thus leading to refractory wound.
OBJECTIVE: To observe the effects of topical application of low-dose insulin on diabetes refractory wound healing.
METHODS: Rats were randomly divided into experimental group and control group: rats in the control group were fed with regular diet and those in the experimental group were fed with high-carbohydrates-fat diet. Rats in the experimental group received intraperitoneal injection of streptozotocin to induce diabetic models. Wounds were made on the back of the rats. The rats in the control group received no treatment, while rats in the experimental group were divided into model group, Vaseline group and insulin group. Wounds in the Vaseline group and insulin group were treated with Vaseline and a small dose of insulin, respectively.
RESULTS AND CONCLUTION: The success rate of induction for diabetes in the experimental group was almost 100%. Complete epithelialization time of the wounds in the model group, Vaseline group and insulin group was longer that than that in the control group (P < 0.05). Compared with the model group and the Vaseline group, the wound healing rate of rats in the insulin group was increased significantly with higher epithelialization degree, the density of collagen fibers was increased and arranged in regular, and the degree of vascularization was increased. The results indicate that topical application of low dose insulin can promote the epithelialization, collagen deposition and angiogenesis, thus accelerating diabetic wound healing.

Key words: tissue construction, skin tissue construction, diabetes, refractory wound, wound healing, high-carbohydrates-fat diet, low dose of insulin, Vaseline, streptozotocin, National Natural Science Foundation of China

CLC Number:

R318

Wang Fang, Li Yong, Su Ying-jun, Wang Na, Xu Chen, Zhou Bo. Application of low-dose insulin in diabetes refractory wound healing: Epithelialization, collagen deposition and angiogenesis [J]. Chinese Journal of Tissue Engineering Research, 2013, 17(20): 3650-3657.

Figures/Tables 7

References

[1] Sun XL, Shi S, He YZ. Guoji Waike Xue Zazhi. 2008;35(10): 681-683.孙晓磊,施森,何延政.糖尿病创面难愈机制的研究进展[J].国际外科学杂志,2008,35(10):681-683.

[2] Fang Y. Shanghai Jiaotong Daxue Xuebao: Yixue Ban. 2009 (12):1403-1406.方勇.创面修复机制及技术研究进展[J].上海交通大学学报:医学版,2009(12):1403-1406.

[3] Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005;366(9498):1736-1743.

[4] Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, et al. The global burden of diabetic foot disease. Lancet. 2005;366 (9498):1719-1724.

[5] Sen CK, Gordillo GM, Roy S, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763-771.

[6] Lima MH, Caricilli AM, de Abreu LL, et al. Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways: a double-blind placebo-controlled clinical trial. PLoS One. 2012;7(5):e36974.

[7] Andreassen TT, Oxlund H. The influence of experimental diabetes and insulin treatments on the biochemical properties of rat skin incisional wounds. Acta Chir Scand. 1987;153(7-8): 405-409.

[8] Jermendy G. Intensive insulin therapy in type 2 diabetes mellitus. Orv Hetil. 2012;153(38):1487-1493.

[9] Wertheimer E, Spravchikov N, Trebicz M, et al. The regulation of skin proliferation and differentiation in the IR null mouse: implications for skin complications of diabetes. Endocrinology. 2001;142(3):1234-1241.

[10] Goodson WH 3rd, Hung TK. Studies of wound healing in experimental diabetes mellitus. J Surg Res. 1977;22(3): 221-227.

[11] Rezvani O, Shabbak E, Aslani A, et al. A randomized, double-blind, placebo-controlled trial to determine the effects of topical insulin on wound healing. Ostomy Wound Manage. 2009;55(8):22-28.

[12] Grotendorst GR, Martin GR, Pencev D, et al. Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. J Clin Invest. 1985;76(6):2323- 2329.

[13] Jin YF, Chen SZ. Xiandai Zhongliu Yixue. 2009;17(12): 2274-2276.金玉峰,陈绍宗.胰岛素促进慢性创面愈合的效果及机制[J].现代肿瘤医学,2009,17(12):2274-2276.

[14] Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001; 50(6):537-546.

[15] Sun N, Yang G, Zhao H, et al. Multidose streptozotocin induction of diabetes in BALB/c mice induces a dominant oxidative macrophage and a conversion of TH1 to TH2 phenotypes during disease progression. Mediators Inflamm. 2005;2005(4):202-209.

[16] Ren J, Zeng HF, Li Y, et al. Zhongguo Meirong Yixue. 2010; 19(5):691-699.任静,曾海峰,栗勇,等.热休克蛋白90促进糖尿病创面愈合的作用研究[J].中国美容医学,2010,19(5):691-699.

[17] Zhang Y, Li HY, Dong L, et al. Zhonghua Tangniaobing Zazhi. 2011;3(5):433-435.张毅,李慧颖,董玲,等.链脲佐菌素诱导模拟2型糖尿病动物模型的研究进展[J].中华糖尿病杂志,2011,3(5):433-435.

[18] Li WJ, Li B, Kou CG, et al. Jilin Daxue: Yixue Ban. 2004;30(6): 991-993.李文君,李波,寇长贵,等.非胰岛素依赖型糖尿病易感基因定位研究进展[J].吉林大学学报：医学版,2004,30(6):991-993.

[19] Li CF,Lu Y, Chen XL, et al. Zhongguo Sunshang yu Xiufu Zazhi. 2012;7(1):54-61.李超飞,刘琰,陈雪莲,等.局部应用胰岛素对糖尿病小鼠创面愈合的影响[J].中国损伤与修复杂志,2012,7(1):54-61.

[20] Lin TS, Abd Latiff A, Abd Hamid NA, et al. Evaluation of topical tocopherol cream on cutaneous wound healing in streptozotocin-induced diabetic rats. Evid Based Complement Alternat Med. 2012;2012:491027.

[21] Rodrigues Filho OA, Fazan VP. Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats. J Neurosci Methods. 2006;151(2):131-138.

[22] Jia WP, Xiang KS. Zhongguo Neifenmi Daixie Zazhi. 2005; 21(3):159-162.贾伟平,项坤三.胰岛β细胞功能评估-从基础到临床[J].中国内分泌代谢杂志,2005,21(3):159-162.

[23] Madibally SV, Solomon V, Mitchell RN, et al. Influence of insulin therapy on burn wound healing in rats. J Surg Res. 2003;109(2):92-100.

[24] Eldad A, Weinberg A, Breiterman S, et al. Early nonsurgical removal of chemically injured tissue enhances wound healing in partial thickness burns. Burns. 1998;24(2):166-172.

[25] Liu Y, Petreaca M, Martins-Green M. Cell and molecular mechanisms of insulin-induced angiogenesis. J Cell Mol Med. 2009;13(11-12):4492-4504.

[26] Apikoglu-Rabus S, Izzettin FV, Turan P, et al. Effect of topical insulin on cutaneous wound healing in rats with or without acute diabetes. Clin Exp Dermatol. 2010;35(2):180-185.

[27] Teoh SL, Latiff AA, Das S. The effect of topical extract of Momordica charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with diabetes induced by streptozotocin. Clin Exp Dermatol. 2009;34(7):815-822.