Local injection of insulin‐zinc stimulates DNA synthesis in skin donor site wound

Our group has reported the ability of local insulin‐zinc injection to accelerate skin wound healing. This experiment was conducted to investigate the metabolic mechanisms of locally injected insulin‐zinc in accelerating wound healing. A partial thickness skin donor site wound was created on the back, and indwelling catheters were placed in the carotid artery and jugular vein in anesthetized rabbits. On day 7 after injury, the wound was either injected with 0.2 U of insulin‐zinc, 0.4 μg zinc (the amount of zinc in 0.2 U of insulin‐zinc), or not injected; stable isotope tracers were infused for measurement of wound DNA synthetic rate as a reflection of cell proliferation. Wound protein synthetic and breakdown rates were also measured. The local insulin‐zinc injection increased wound insulin concentration from below 5 pmol/L to 1,260±780 pmol/L with minor changes in blood glucose concentration that did not require exogenous glucose replacement. In the insulin‐zinc–injected wound, the total DNA synthetic rate was increased by ∼50% ( p <0.05 vs. control). In the zinc‐injected wound, whereas total DNA synthetic rate was increased ( p <0.05 vs. control), net protein deposition (synthesis–breakdown) was less ( p <0.05) than those in the control and insulin‐zinc groups. We conclude that local insulin‐zinc injection stimulates wound DNA synthesis, which would be expected to accelerate wound reepithelialization.