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.