Topical Insulin Modulates Inflammatory and Proliferative Phases of Burn-Wound Healing in Diabetes-Induced Rats.

The healing time of burn wounds depends on surface area and depth of the burn and associated comorbidities. Diabetes mellitus (DM) causes delays in the healing process by extending the inflammatory phase. Treatment with topical insulin can improve the inflammatory phase, restore metabolic dysregulation, and modulate impaired cellular signaling in burn wounds. The objective of this study was to evaluate markers of the inflammatory and proliferative phases of second-degree burns after topical insulin treatment in diabetic rats. Type I DM was induced with streptozotocin in male Wistar rats. The animals' backs were shaved and subjected to thermal burning. Rats were randomized into two groups: control diabetic (DC) and insulin diabetic (DI). At Days 7 and 14 postburn, rats were euthanized, and wound-tissue sections were evaluated by hematoxylin and eosin, Weigert, and Verhöeff staining, immunohistochemistry-paraffin, and enzyme-linked immunosorbent assay. A significant increase in reepithelialization was seen on Days 7 and 14 in DI versus DC rats. On Day 7, interleukin (IL)-1ß, IL-6, monocyte chemotactic protein (MCP)-1, and F4/80 expression were increased in DI versus DC rats. On Day 14, MCP-1 expression was decreased and F4/80 increased in DI versus DC rats. On Days 7 and 14, Ki-67, transforming growth factor-ß1, vascular endothelial growth factor expression, and formation of elastic fibers were increased in DI versus DC rats. Topical insulin modulates burn-wound healing in diabetic animals by balancing inflammation and promoting angiogenesis and formation of elastic fibers.

Insulin signaling pathway in the masseter muscle of dexamethasone-treated rats.

BACKGROUND AND AIMS: The treatment with glucocorticoids may induce molecular changes in the level and/or degree of phosphorylation of proteins located downstream of the insulin receptor/insulin-like growth factor receptor (IR/IGF1R) in many tissues. However, few studies have investigated the intracellular insulin pathway in the masseter muscle. Therefore, this study aimed to analyze the IR/IGF1R signaling pathway in the masseter muscle of rats treated with dexamethasone. MATERIALS AND METHODS: Male Wistar rats were divided into two groups: control group (intraperitoneally injected with 0.9% NaCl solution) and dexamethasone group [intraperitoneally injected with 1 mg/kg (bw) dexamethasone solution] for 10 consecutive days. Sections of the masseter muscle were removed at time zero and after the infusion of regular insulin into the portal vein. RESULTS: Dexamethasone administration induces body weight loss without changing masseter muscle weight and reduces the expression of total IR and PI3K proteins; total levels of IRS1, Akt, and ERK1 remain unchanged between groups. The degree of phosphorylation/activity of IRS1 after insulin stimulus increased only in the control group; degree of phosphorylation of Akt increased in both groups, but this increase was attenuated in the dexamethasone group. DISCUSSION AND CONCLUSION: The degree of phosphorylation/activity in the masseter muscle is different from that in other muscle territories.

DHEA and non-alcoholic fat liver disease: increased gene expression of peroxisome proliferation-activated receptor γ (PPARγ) and fatty acid synthase (FAS) / DHEA e doença gordurosa hepática não-alcoólica: aumento na expressão gênica do peroxisome proliferation-activated receptor γ (PPARγ) e ácido graxo sintase (FAS)

Dehydroespiandrosterone (DHEA) is associated with improvements in chronic degenerative diseases, including obesity, insulin resistance, and cardiovascular diseases. Nevertheless, it is observed an increase in its concentration in individuals with liver lipid infiltration, but it is not precise if this condition emerges as a cause or a consequence. In this way, we aimed to identify gene expression alterations in lipid and glucose liver metabolism markers, as well as oxidative stress markers. For this purpose, male Wistar rats, 12-14 months old were treated with subcutaneous injections of DHEA (only dose of 10 mg kg-1); and after 7 days, hepatic gene expression by PCR real time were performed for the following genes: G6Pase, PEPCK, FAS, PPARγ, malic enzyme, ChREBP, LXR, catalase, GPx, iNOS, NADPH oxidase subunits and PCNA. We observed a tendency of reduction in G6Pase gene expression in treated group (p = 0.08). In addition, it was identified an increase in liver PPARγ and FAS gene expressions, two markers of increased activity of lipogenic pathway. We also observed an increase in iNOS gene expression, a known inductor of systemic and hepatic insulin resistance. In conclusion, our data indicates that the treatment with DHEA can be associated with the development of liver lipid infiltration and hepatic insulin resistance.

A deidroepiandrosterona (DHEA) encontra-se associada a melhorias em quadros de obesidade, resistência à insulina e doenças cardiovasculares. Porém, observa-se um aumento na sua concentração em indivíduos portadores de infiltração lipídica hepática, mas sem saber precisar se o mesmo surge como causa ou consequência. Assim, objetivamos identificar alterações na expressão gênica hepática de marcadores relacionados ao metabolismo lipídico e glicídico e de estresse oxidativo. Para tanto, ratos machos com 12-14 meses de idade foram tratados com injeção subcutânea de DHEA (dose única 10 mg kg-1), e após 7 dias foram feitas análises da expressão gênica hepática por PCR em tempo real das seguintes proteínas: G6Pase, PEPCK, FAS, PPARγ, enzima málica, ChREBP, LXR, catalase, GPx, iNOS, subunidades da NADPHoxidase e PCNA. Observamos uma tendência à redução da expressão gênica da G6Pase no grupo tratado (p = 0,08). Também identificamos um aumento na expressão gênica hepática do PPARγ e FAS, dois indicadores de aumento da atividade das vias de lipogênese. Observamos um aumento na expressão gênica da iNOS, um conhecido agente indutor de resistência insulina sistêmica e hepática. Em conclusão, nossos dados indicam que o tratamento com DHEA pode estar associado com o desenvolvimento de um quadro de infiltração lipídica hepática e resistência à insulina hepática.