106 Local Injection of Insulin-Zinc Suspension Stimulates DNA Synthesis in Skin Donor Wound

Abstract

We have previously reported that local injection of small doses of long-acting insulin-zinc suspension maintained sufficiently high insulin concentration in the wound fluid and accelerated the healing. The present experiment was to measure the rates of cell proliferation (reflected by DNA synthesis) and protein metabolism in the wound. These are the underlying metabolic processes responsible for the healing. Partial thickness skin donor wound was created on the back and indwelling catheters were placed in the carotid artery and jugular vein in adult rabbits under general anesthesia. The wound was covered with Aquaphor gauze, OpSite membrane, and surgical gauze. On day 7 after wounding, the wound was either injected with 0.2 units of insulin-Zn, Zn alone, or no injection; stable isotopes were infused into the jugular vein catheter in conscious rabbits for measurement of DNA synthesis, protein synthesis and breakdown in the wound. The local insulin-Zn injection raised wound insulin concentration to 168 ± 39 μU/ml. In contrast, in the control and Zn groups wound insulin concentrations were below the detectable level. The local injection of insulin-Zn suspension increased (p = 0.03) DNA synthesis in the wound with minor changes in blood glucose concentration which did not require exogenous glucose replacement. In the Zn group, whereas the rate of DNA synthesis tended to increase (p = 0.051 vs. control), the protein net balance (synthesis – breakdown) was lower (p < 0.05) than those in the control and insulin-Zn (Table 1). We conclude that local injection of a small dose (0.2 units insulin) long-acting insulin-Zn suspension stimulated wound DNA synthesis without major systemic side effects thereby providing an effective and safe approach to accelerate wound healing. Although local Zn injection might also stimulate wound DNA synthesis, the benefit on the healing process was limited by decreased net protein deposition. Table 1. Wound DNA and protein metabolism. DNA synthesis Protein synthesis Protein net balance Values are means ± SD in %/d. * p < 0.05 vs. control; + p = 0.051 vs. control;#, p < 0.05 vs. control and insulin-Zn by one-way ANOVA. Control (n = 7) 2.9 ± 0.9 20.5 ± 8.4 7.9 ± 6.0 Insulin-Zn (n = 7) 4.2 ± 0.9* 17.9 ± 8.2 9.4 ± 6.4 Zn (n = 7) 4.1 ± 0.9+ 13.0 ± 5.8 −0.2 ± 3.4#