Differential expression and localization of insulin-like growth factors I and II in cutaneous wounds of diabetic and nondiabetic mice

David L. Brown, Christine D. Kane, Steven D. Chernausek, David G Greenhalgh

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Insulin-like growth factor (IGF)-I has profound effects on tissue repair. IGF-II is felt to exert its influence predominately during fetal development. The purpose of this study was to localize and quantify the expression of IGF-I and IGF-II mRNA and protein during early wound healing in diabetic and nondiabetic mice. The hypothesis is that IGF-I and IGF-II are upregulated in the healing wound but their expression is inhibited in diabetics. Full-thickness cutaneous wounds were made on genetically diabetic (C57BL/KsJ-db/db) mice and their nondiabetic littermates. At various times after wounding, one-half of each wound was fixed and paraffin embedded for immunohistochemistry and in situ hybridization. The other half was flash- frozen for quantification of IGF mRNA by competitive reverse transcriptase polymerase chain reaction and protein by radioimmunoassay. IGF-I mRNA rose sharply in nondiabetics at day 3. Expression in diabetic wounds was significantly delayed until 14 days after wounding. Even then, diabetic IGF- I mRNA levels were 50% less than those in the nondiabetics at their peak. Although not usually considered active in adult life, IGF-II mRNA expression was augmented after wounding, peaking at 3 days in nondiabetics. As with IGF- I, diabetic wounds exhibited a delay in IGF-II mRNA expression, with maximal levels at 10 days after wounding. Interestingly, peak concentrations of IGF- II mRNA were four times greater in diabetics versus nondiabetics. Trends in IGF-I protein expression followed the patterns of mRNA expression. IGF-I levels in nondiabetics were initially double those in diabetics and peaked at 5 days. Diabetic wound concentrations of IGF-I did not peak until 21 days after wounding, at which time they rose to nondiabetic levels. IGF-I and IGF- II proteins were localized to the advancing epithelial edge, to the epithelial cells of adjacent hair follicles, and to the granulation tissue of the wounds. IGF-I and IGF-II mRNA expression was noted in the epithelial edge and in the hair follicles adjacent to the wound, paralleling protein expression. Both IGF-I and IGF-II are up-regulated in the healing wound. A delay in IGF-I and -II presence is noted in the diabetic wound. The impairment in tissue repair in diabetic animals is at least partially due to a deficiency in the production of the IGFs.

Original languageEnglish (US)
Pages (from-to)715-724
Number of pages10
JournalAmerican Journal of Pathology
Issue number3
StatePublished - Sep 1997
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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