Lack of insulin-like growth factor 1 (IGF1) in the basal keratinocyte layer of diabetic skin and diabetic foot ulcers

Abstract

Wound healing, including re-epithelialization, is delayed in diabetes. Growth factors influence the healing process and amongst these, insulin-like growth factor (IGF) has been shown to stimulate keratinocyte proliferation in vitro. Monoclonal antibodies to insulin-like growth factors 1 and 2 (IGF1 and IGF2) were used to investigate their distribution in diabetic foot ulcers and surrounding tissues by immunohistochemistry, compared with diabetic and non-diabetic uninjured skin. IGF2 was found throughout the epidermis (stratum granulosum, spinosum, and basale) in all three groups. Staining for IGF2 was intense in both normal and diabetic skin as well as in diabetic foot ulcers, being greatest at the ulcer edge. IGF1, in comparison, was found throughout the epidermis of non-diabetic skin; expression was restricted to the stratum granulosum and spinosum of uninjured diabetic skin and was absent in the basal layer at the ulcer edge. A similar absence of IGF1 in dermal fibroblasts was found in tissue sections from diabetic patients. This lack of expression of IGF1 within the basal layer and fibroblasts may contribute to retarded wound healing in diabetes mellitus.