Liver insulin-like growth factor-1 mediates effects of low-intensity vibration on wound healing in diabetic mice

Rita E. Roberts, Jacqueline Cavalcante-Silva, Mercedes Del Rio-Moreno, Onur Bilgen, Rhonda D. Kineman, Timothy J. Koh

Research output: Contribution to journalArticlepeer-review


Chronic wounds in diabetic patients are associated with significant morbidity and mortality; however, few therapies are available to improve healing of diabetic wounds. Our group previously reported that low-intensity vibration (LIV) could improve angiogenesis and wound healing in diabetic mice. The purpose of this study was to begin to elucidate the mechanisms underlying LIV-enhanced healing. We first demonstrate that LIV-enhanced wound healing in db/db mice is associated with increased IGF1 protein levels in liver, blood, and wounds. The increase in insulin-like growth factor (IGF) 1 protein in wounds is associated with increased Igf1 mRNA expression both in liver and wounds, but the increase in protein levels preceded the increase in mRNA expression in wounds. Since our previous study demonstrated that liver was a primary source of IGF1 in skin wounds, we used inducible ablation of IGF1 in the liver of high-fat diet (HFD)-fed mice to determine whether liver IGF1 mediated the effects of LIV on wound healing. We demonstrate that knockdown of IGF1 in liver blunts LIV-induced improvements in wound healing in HFD-fed mice, particularly increased angiogenesis and granulation tissue formation, and inhibits the resolution of inflammation. This and our previous studies indicate that LIV may promote skin wound healing at least in part via crosstalk between the liver and wound.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalJournal of Pathology
Issue number1
StatePublished - May 2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine


  • chronic wound
  • diabetes complications
  • impaired wound healing
  • insulin-like growth factors
  • mechanical therapy
  • skin wound healing
  • skin–liver axis
  • vibration therapy


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