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-1α 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. Trial Registration: ClinicalTrials.gov NCT01295177

The actions of LH are mediated through a single class of cell surface LH/human chorionic gonadotropin receptor, which is a member of the G protein-coupled receptor family. In the present study we showed that LH induced rapid tyrosine phosphorylation and activation of the Janus kinase 2 (JAK2) in rat ovary. Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. In addition, LH induced IRS-1/phosphoinositol 3-kinase and Shc /growth factor receptor-binding protein 2 (Grb2) associations and downstream AKT (protein kinase B, homologous to v-AKT) serine phosphorylation and ERK tyrosine phosphorylation, respectively. The simultaneous infusion of insulin and LH induced higher phosphorylation levels of JAK2, STAT5b, IRS-1, and AKT compared with each hormone alone in the whole ovary of normal rats. By immunohistochemistry we demonstrated that these late events take place in follicular cells and both external and internal theca. These results indicate a new signal transduction pathway for LH and show that there is positive cross-talk between the insulin and LH signaling pathways at the level of phosphoinositol 3-kinase/AKT pathway in this tissue.

Background: Photobiomodulation consists of inducing healing by irradiating light. This scoping review investigates the effect of blue light on the healing process. Methods: The MEDLINE, Web of Science, Scopus, and CINAHL databases were searched. Two reviewers independently examined the search results and extracted data from the included studies. A descriptive analysis was performed. Results: Twenty-two articles were included. Studies were categorized as in vitro/mixed, preclinical, and clinical. The power density used was 10–680 mW/cm² in most of the in vitro/preclinical studies, the irradiation time ranged from 5 s to 10 min, and different wavelengths and energy densities were used. In clinical studies, the wavelength ranged from 405 to 470 nm, and the energy density varied from 1.5 to 30 J/cm². Conclusions: A low energy density (<20 J/cm²) was able to stimulate the different cell types and proteins involved in healing, while a high energy density, 20.6–50 J/cm², significantly reduced cell proliferation, migration, and metabolism. There is a great variety of device parameters among studies, and this makes it difficult to conclude what the best technical specifications are. Thus, further studies should be performed in order to define the appropriate parameters of light to be used.

The healing process is complex in diabetic wounds, and the healing mechanism of burn wounds is different from that of incisional or excisional wounds. Data from our previous study indicated that topical insulin cream reduced wound closure time in diabetic rats. Our aim was to investigate the effect of topical insulin cream on wound healing following second-degree burns in control and diabetic rats. Rats were divided into four groups: control (nondiabetic) rats treated with placebo (CP), control (nondiabetic) rats treated with topical insulin cream (CI), diabetic rats treated with placebo (DP), and diabetic rats treated with topical insulin cream (DI). The wounds were assessed at 4 time points (1, 7, 14, and 26 days) post-wounding for morphometric analysis of wound sections stained with hematoxylin/eosin, α-smooth muscle actin, and Picrosirius red to evaluate general aspects of the wound, inflammatory infiltrate, blood vessels, and Types I and III collagen fibers. Histological analysis showed that topical insulin cream increased the inflammatory cell infiltrate in the DI group (at 7 and 14 days postburn, p < .05) and blood vessels (at 14 days postburn, p < .05) to levels similar to those of groups CP and CI. Wounds treated with topical insulin cream (CI and DI groups) showed significantly stronger staining for fibrillar collagen than wounds of the DP group. The use of topical insulin may reduce the duration of the inflammatory phase; improve wound reepithelialization, tissue granulation, and wound contraction; and increase collagen deposition in second-degree burns in healthy and diabetic animals.

Purpose. Insulin has been acknowledged as a mediator of several physiological events in lacrimal and salivary glands. We investigated the presence of insulin receptors and of insulin-induced autoph...