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Tissue Repair in Models of Diabetes Mellitus

A Review

  • Protocol
Wound Healing

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 78))

Abstract

Diabetes mellitus is a major cause of impaired tissue repair. Patients with this disease not only have a propensity to develop wounds, but when they do, they tend to have difficulty healing those wounds. Simple wounds often become chronic and infectious wound complications are not uncommon. Unfortunately, the amputation rate for diabetics is much higher than for the nondiabetic population. Because healing problems are so common and devastating, several models of tissue repair have been developed in animals that are “made” diabetic or have a genetic predisposition for diabetes mellitus. The goal of this chapter is to review these models and to try to relate their similarities to human diabetes mellitus. It must be remembered, however, that diabetes mellitus is a very complex spectrum of diseases and that no animal model completely represents all human forms. It is important to choose a model that answers the question that the investigator is asking. By understanding how the various models relate to different aspects of human diabetes mellitus, the investigator can choose the correct model for the proposed studies.

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References

  1. McMurry, J. F. Jr. (1984) Wound healing with diabetes mellitus. Surg. Clin. North Am. 64, 769–778.

    PubMed  Google Scholar 

  2. Goodson, W. H. III and Hunt, T. K. (1979) Wound healing and the diabetic patient. Surg. Gynecol. Obstet. 149, 600–608.

    PubMed  Google Scholar 

  3. Economides, P. A. and Veves, A. (2000) Etiopathogenesis of foot ulceration in diabetes. Wounds 12, 3b–6b.

    Google Scholar 

  4. Boulton, A. J. and Vileikyte, L. (2000) Pathogenesis of diabetic foot ulceration and measurements of neuropathy. Wounds 12, 12b–18b.

    Google Scholar 

  5. Engerman, R. L. and Kramer, J. W. (1982) Dogs with induced or spontaneous diabetes as models for the study of human diabetes mellitus. Diabetes 31, 26–29.

    PubMed  CAS  Google Scholar 

  6. Catanzaro-Guimaraes, S. A. (1968) Histometric determination of collagen fibers in granulating wounds of alloxan diabetic rats. Experentia 24, 1168,1169.

    Article  Google Scholar 

  7. Rerup, C. C. (1970) Drugs producing diabetes through damage of insulin secreting cells. Pharmacol. Rev. 22, 485–518.

    PubMed  CAS  Google Scholar 

  8. Grodsky, G. M., Anderson, C. E., Coleman, D. L., et al. (1982) Metabolism and underlying causes of diabetes mellitus. Diabetes 31, 45–53.

    PubMed  CAS  Google Scholar 

  9. Goodson, W. H. III and Hunt, T. K. (1977) Studies of wound healing experimental diabetes mellitus. J. Surg. Res. 22, 221–227.

    Article  PubMed  Google Scholar 

  10. Seifter, E., Rettura, G., Padawer, J., et al. (1981) Impaired wound healing in streptozotocin diabetes: prevention by supplemental vitamin A. Ann. Surg. 194, 42–50.

    Article  PubMed  CAS  Google Scholar 

  11. Grotendorst, G. R., Martin, G. R., Pencev, D., et al. (1985). Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. J. Clin. Invest. 76, 2323–2329.

    Article  PubMed  CAS  Google Scholar 

  12. Andreassen, T. T. and Oxlund, H. (1987) The influence of experimental diabetes and insulin treatments on the biomechanical properties of rat skin incisional wounds. Acta Chir. Scand. 153, 405–409.

    PubMed  CAS  Google Scholar 

  13. Soriano, F. G., Virag, L., Jagtap, P., et al. (2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat. Med. 7, 108–113.

    Article  CAS  Google Scholar 

  14. Riley, W. J., McConnell, T. J., McClaren, N. K., et al. (1981) The diabetogenic effects of streptozotocin in mice are prolonged and inversely related to age. Diabetes 30, 718–723.

    Article  PubMed  CAS  Google Scholar 

  15. Coleman, D. M. (1982) Other potentially useful rodent models for the study of human diabetes mellitus. Diabetes 31, 24,25.

    Article  PubMed  CAS  Google Scholar 

  16. Stauffacher, W., Orci, L., Cameron, D. P., et al. (1970) Spontaneous hyperglycemia and/or obesity in laboratory rodents. Recent Prog. Hormone Res. 27, 41–95.

    Google Scholar 

  17. Leiter, E. H., Prochazka, M., and Coleman, D. L. (1987) Animal model of human disease: the non-obese diabetic (NOD) mouse. Am. J. Pathol. 128, 380–383.

    PubMed  CAS  Google Scholar 

  18. Lieter, E. H. (1989) The genetics of diabetes susceptibility in mice. FASEB J. 3, 2231–2241.

    Google Scholar 

  19. Like, A. A., Butler, L., Williams, R. M., et al. (1982) Spontaneous autoimmune diabetes mellitus in the BB rat. Diabetes 31, 7–13.

    Article  PubMed  CAS  Google Scholar 

  20. Gerritsen, G. C. (1982) The Chinese hamster as a model for the study of diabetes mellitus. Diabetes 31, 14–23.

    PubMed  CAS  Google Scholar 

  21. Phillips, R. W., Panepinto, L. M., Spangler, R., and Westmoreland, N. (1982) Yucatan swine as a model of human diabetes mellitus. Diabetes 31, 30–36.

    Article  PubMed  CAS  Google Scholar 

  22. Howard, C. F. Jr. (1982) Nonhuman primates as models for the study of human diabetes mellitus. Diabetes 31, 37–42.

    Article  PubMed  Google Scholar 

  23. Rabinovitch, A. (2000) Autoimmune diabetes mellitus. Sci. Med. 7, 18–27.

    CAS  Google Scholar 

  24. Coleman, D. L. (1982) Diabetes-obesity syndromes in mice. Diabetes 31, 1–6.

    Article  PubMed  CAS  Google Scholar 

  25. Bray, G. A. and York, D. A. (1979) Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol. Rev. 59, 719–791.

    PubMed  CAS  Google Scholar 

  26. Spiegelman, B. M. and Flier, J. S. (1996) Adipogenesis and obesity: rounding out the big picture. Cell 87, 377–389.

    Article  PubMed  CAS  Google Scholar 

  27. Caro, J. F., Sinha, M. K., Kolaczynski, J. W., et al. (1996) Leptin: the tale of an obesity gene. Diabetes 45, 1455–1462.

    PubMed  CAS  Google Scholar 

  28. Coleman, D. L. and Hummel, K. P. (1967) Studies with the mutation diabetes in the mouse. Diabetologia 3, 238–248.

    Article  PubMed  CAS  Google Scholar 

  29. Coleman, D. L. and Hummel, K. P. (1969) Effects of parabiosis of normal with genetically diabetes in mice. Am. J. Physiol. 217, 1298–1304.

    PubMed  CAS  Google Scholar 

  30. Zhang, Y., Proenca, R., Maffei, M., et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.

    Article  PubMed  CAS  Google Scholar 

  31. Considine, R. V., Considine, E. L., Williams, C. J., et al. (1996) Mutation screening and identification of a sequence variation in the human Ob gene coding. Biochem. Biophys. Res. Commun. 220, 735–739.

    Article  PubMed  CAS  Google Scholar 

  32. Tartaglia, L. A., Dembrski, M., Weng, X., et al. (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 1263–1271.

    Article  PubMed  CAS  Google Scholar 

  33. Goodson, W. H. III and Hunt, T. K. (1979) Deficient collagen formation by obese mice in a standard wound model. Am. J. Surg. 138, 692–694.

    Article  PubMed  CAS  Google Scholar 

  34. Goodson, W. H. III and Hunt, T. K. (1986) Wound collagen accumulation in obese hyperglycemic mice. Diabetes 35, 491–495.

    Article  PubMed  CAS  Google Scholar 

  35. Greenhalgh, D. G., Sprugel, K. H., Murray, M. J., and Ross, R. (1990) PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am. J. Pathol. 136, 1235–1246.

    PubMed  CAS  Google Scholar 

  36. Albertson, S., Hummel, R. P. III, Breeden, M., and Greenhalgh, D. G. (1993) PDGF and FGF reverse the healing impairment in protein malnourished diabetic mice. Surgery 114, 368–373.

    PubMed  CAS  Google Scholar 

  37. Greenhalgh, D. G., Hummel, R. P. III, Albertson, A., and Breeden, M. P. (1993) Synergistic actions of platelet-derived growth factor and the insulin-like growth factors in vivo. Wound Rep. Reg. 1, 69–81.

    Article  CAS  Google Scholar 

  38. Brown, R. L., Breeden, M. P., and Greenhalgh, D. G. (1994) PDGF and TGF-α act synergistically to improve healing in the genetically diabetic mouse. J. Surg. Res. 56, 562–570.

    Article  PubMed  CAS  Google Scholar 

  39. Tsuboi, R. and Rifkin, D. B. (1990) Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice. J. Exp. Med. 172, 245–251.

    Article  PubMed  CAS  Google Scholar 

  40. Klingbeil, C. K., Cesar, L. B., and Fiddes, J. C. (1991) Basic fibroblast growth factor accelerates tissue repair in models of impaired wound healing. Prog. Clin. Biol. Res. 365, 443–458.

    PubMed  CAS  Google Scholar 

  41. Werner, S., Breeden, M., Greenhalgh, D. G., Hofschneider, P. H., and Longaker, M. T. (1994) Induction of keratinocyte growth factor is reduced and delayed during wound healing in the genetically diabetic mouse. J. Invest. Dermatol. 103, 469–472.

    Article  PubMed  CAS  Google Scholar 

  42. Frank, S., Hubner, G., Breier, G., Longaker, M. T., Greenhalgh, D. G., and Werner, S. (1995) Regulation of vascular endothelial growth factor expression in cultured keratinocytes. J. Biol. Chem. 270, 12,607–12,613.

    Article  PubMed  CAS  Google Scholar 

  43. Brown, D. L., Kane, C. D., Chernausek, S. D., and Greenhalgh, D. G. (1997) Differential expression and localization of IGF-I and IGF-II in cutaneous wounds of diabetic versus nondiabetic mice. Am. J. Pathol. 151, 715–724.

    PubMed  CAS  Google Scholar 

  44. Neely, A. N., Clendening, C. E., Gardner, J., and Greenhalgh, D. G. (2000) Gelatinase activities in wounds of healing-impaired mice versus non-healing-impaired mice. J. Burn Care Rehabil. 21, 395–402.

    Article  PubMed  CAS  Google Scholar 

  45. Ksander, G. A., Ogawa, Y. A. M., Chu, G. H., et al. (1990) Exogenous transforming growth factor-beta 2 enhances connective tissue formation and wound strength in guinea pig dermal wounds by secondary intent. Ann. Surg. 211, 288–294.

    PubMed  CAS  Google Scholar 

  46. Holder, I. A., Brown, R. L., and Greenhalgh, D. G. (1997) Animal models to study wound closure and topical treatment of infected wounds in the healing impaired and normohealing host. Wound Rep. Reg. 5, 198–204.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Surgery, University of California, Davis, CA

    David G. Greenhalgh

  2. Shriners Hospitals for Children Northern California, Sacramento, CA

    David G. Greenhalgh

Authors
  1. David G. Greenhalgh
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Editor information

Editors and Affiliations

  1. Department of Surgery, Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, IL

    Luisa A. DiPietro  & Aime L. Burns  & 

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© 2003 Humana Press Inc., Totowa, NJ

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Greenhalgh, D.G. (2003). Tissue Repair in Models of Diabetes Mellitus. In: DiPietro, L.A., Burns, A.L. (eds) Wound Healing. Methods in Molecular Medicine™, vol 78. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-332-1:181

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  • DOI: https://doi.org/10.1385/1-59259-332-1:181

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-0-89603-999-5

  • Online ISBN: 978-1-59259-332-3

  • eBook Packages: Springer Protocols

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