Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial

Background: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. Objective: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. Research Design and Methods: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing. Results and Conclusions: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1 alpha in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.Sao Paulo Research Foundation (FAPESP)Sao Paulo Research Foundation (FAPESP)National Institute of Science and Technology (INCT)National Institute of Science and Technology (INCT)National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq

A prolonged interval between deep intestinal ischemia and anastomotic construction does not impair wound strength in the rat.

Contains fulltext : 51827.pdf (publisher's version ) (Closed access)INTRODUCTION: Transient intestinal ischemia can reduce anastomotic strength, which poses an increased risk of complications. The objective of this study is to establish if a prolonged interval between profound ischemia and construction of an anastomosis affects anastomotic strength. METHODS: Male Wistar rats were used: in experimental groups, profound mesenteric ischemia was induced by clamping both superior mesenteric artery and more distal arteries in the ileal mesentery. Resection and anastomosis in ileum and colon were performed immediately (IR0) or 24 h after releasing the clamps (IR24). In controls (C0 and C24), arteries were not clamped. After 5 days, anastomotic bursting pressure (BP), breaking strength (BS), and hydroxyproline were measured, and histological analysis was performed. RESULTS: Mortality and anastomotic dehiscence rates were significantly higher in IR0 compared to C0. In ileum, the BS was 34% lower (p<0.05) in IR0 compared to C0, while there were no significant differences in BS or BP between the IR24 and C24 groups. In colon anastomoses, although no differences in BS and BP were found, bursting site was at the anastomosis in 82% in group IR0 vs 30% in group C0, reflecting reduced anastomotic strength in the former. Again, after 24 h, there were no differences between IR and C group. Hydroxyproline and histology were not different between groups. CONCLUSIONS: Extending the interval between transient deep intestinal ischemia and construction of an anastomosis does not impair wound strength