Insulin Promotes Wound Healing by Inactivating NFkβ P50/P65 and Activating Protein and Lipid Biosynthesis and alternating Pro/Anti-inflammatory Cytokines Dynamics

Abstract

Four hundred and twenty-two million people have diabetes due to excess free body glucose in their body fluids. Diabetes leads to various problems including retinopathy, neuropathy, arthritis, damage blood vessels etc; it also causes a delay in wound healing. Insufficiency of insulin is the main reason for diabetes-I and systemic insulin treatment is a remedy. The perspective of the potential use of insulin/insulin based drugs to treat chronic wounds in diabetic conditions is focused on in this review. At the site of the wound, TNF-α, IFN-γ, IL-1β and IL-6 pro-inflammatory cytokines cause the generation of free radicals, leading to inflammation which becomes persistent in diabetes. Insulin induces expression of IL-4/IL-13, IL-10 anti-inflammatory cytokines etc which further down-regulates NFkβ P50/P65 assembly. Insulin shifts the equilibrium towards NFkβ P50/P50 which leads to down-regulation of inflammatory cytokines such as IL-6, IL-10 etc through STAT6, STAT3 and c-Maf activation causing nullification of an inflammatory condition. Insulin also promotes protein and lipid biosynthesis which indeed promotes wound recovery. Here, in this article, the contributions of insulin in controlling wound tissue microenvironments and remodulation of tissue have been summarised, which may be helpful to develop novel insulin-based formulation(s) for effective treatment of wounds in diabetic conditions.