Beneficial effects of physical exercise for ß-cell maintenance in a type 1 diabetes mellitus animal model.

NEW FINDINGS: What is the central question of this study? Type 1 diabetes mellitus (T1D) leads to hyperglycaemia owing to pancreatic ß-cell destruction by the immune system. Physical exercise has been shown to have potentially beneficial protective roles against cytokine-induced pancreatic ß-cell death, but its benefits are yet to be proved and should be understood better, especially in the islet environment. What is the main finding and its importance? Physical exercise protects against ß-cell loss in a well-described animal model for T1D, induced by multiple low doses of streptozotocin. This seems to be related to reduced cytokine-induced ß-cell death and increased islet cell proliferation. Contributions of islet neogenesis and/or transdifferentiation of pancreatic non-ß-cells into ß-cells cannot be excluded. ABSTRACT: Physical exercise has beneficial effects on pancreatic ß-cell function and survival in a pro-inflammatory environment. Although these effects have been linked to decreased islet inflammation and modulation of pro-apoptotic pathways, little is known about the islet microenvironment. Our aim was to evaluate the effects of physical exercise in islet histomorphology in a mouse model of type 1 diabetes mellitus induced by multiple low doses of streptozotocin. As expected, induction of type 1 diabetes mellitus led to ß-cell loss and, consequently, decreased islet area. Interestingly, although the decrease in islet area was not prevented by physical exercise, this was not the case for the decrease in ß-cell mass. This was probably related to induction of ß-cell regeneration, because we observed increased proliferation and regeneration markers, such as Ki67 and Pcna, in islets of trained mice. These were found in the central and peripheral regions of the islets. An increase in the percentage of α- and δ-cells in these conditions, combined with an increase in proliferation and Pax4 labelling in peripheral regions, suggest that ß-cell regeneration might also occur by transdifferentiation. This agrees with the presence of cells double stained for insulin and glucagon only in islets of diabetic trained mice. In addition, this group had more extra-islet insulin-positive cells and islets associated with ducts than diabetic mice. Physical exercise also decreased nuclear factor-κB activation in islet cells of diabetic trained compared with diabetic untrained mice, indicating a decrease in pro-inflammatory cytokine-induced ß-cell death. Taken together, these findings indicate that preservation of ß-cell mass induced by physical exercise involves an increase in ß-cell replication and decrease in ß-cell death, together with islet neogenesis and islet cell transdifferentiation.

Synergistic anti-inflammatory effect: simvastatin and pioglitazone reduce inflammatory markers of plasma and epicardial adipose tissue of coronary patients with metabolic syndrome.

BACKGROUND: The inappropriate secretion of adipocytokines plays a critical role in chronic inflammatory states associated with obesity-linked type 2 diabetes and atherosclerosis. The pleiotropic actions of simvastatin and pioglitazone on epicardial adipose tissue (EAT) are unknown. This study assessed the anti-inflammatory actions of simvastatin and pioglitazone on EAT in patients with coronary artery disease (CAD) and metabolic syndrome (MS). METHODS: A total of 73 patients with multivessel CAD who underwent elective bypass grafting were non-randomly allocated to one of four subgroups: Control (n = 17), simvastatin (20 mg/day, n = 20), pioglitazone (15 mg or 30 mg/day, n = 18), or simvastatin + pioglitazone (20 mg/day + 30 mg/day, respectively, n = 18); 20 valvar patients were also included. EAT samples were obtained during surgery. The infiltration of macrophages and lymphocytes and cytokines secretion were investigated using immunohistochemical staining and compared to plasma inflammatory biomarkers. RESULTS: Simvastatin significantly reduced plasma interleukin-6, leptin, resistin and monocyte chemoattractant protein-1 (p < 0.001 for all); pioglitazone reduced interleukin-6, tumoral necrose factor-alpha, resistin and matrix metalloproteinase-9 (p < 0.001 for all). Simvastatin + pioglitazone treatment further reduced plasmatic variables, including interleukin-6, tumoral necrose factor-alpha, resistin, asymmetric dimethylarginine and metalloproteinase-9 vs. the control group (p < 0.001). Higher plasma adiponectin and lower high sensitivity C-reactive protein concentrations were found simultaneously in the combined treatment group. A positive correlation between the mean percentage systemic and tissue cytokines was observed after treatments. T- and B-lymphocytes and macrophages clusters were observed in the fat fragments of patients treated with simvastatin for the first time. CONCLUSIONS: Pioglitazone, simvastatin or combination treatment substantially reduced EAT and plasma inflammatory markers in CAD and MS patients. These tissue effects may contribute to the control of coronary atherosclerosis progression.

Effects of low-intensity polarized visible laser radiation on skin burns: a light microscopy study.

OBJECTIVE: This study was carried out to investigate the influence of low-intensity polarized visible laser radiation on the acceleration of skin wound healing. BACKGROUND DATA: Low-level laser therapy (LLLT) at adequate wavelength, intensity, and dose can accelerate tissue repair. However, there is still unclear information about light characteristics, such as coherence and polarization. Some studies indicate that linearly polarized light can survive through long propagation distance in biological tissue. MATERIALS AND METHODS: Three burns about 6 mm in diameter were created on the back of rats with liquid N(2). Lesion "L(//)" was irradiated by He-Ne laser (lambda = 632.8 nm), D= 1.0 J/cm(2), with linear polarization parallel to the spinal column of the rat. Lesion "L(inverted v)" was irradiated using the same laser and dose, but the light polarization was aligned perpendicularly to the relative orientation. Lesion "C" was not irradiated in order to be considered as control. The animals were sacrificed at day 3-17 after lesion creation. Samples were collected and prepared for histological analysis. RESULTS: Histological analysis showed that the healing of irradiated wounds was faster than that of non-irradiated wounds. Moreover, it was observed that skin wound repair is dependent on polarization orientation with respect to a referential axis as the animal's spinal column. Consequently, "L(//)" was completely healed after 17 days, whereas "L (perpendicular) " showed a moderate degree of healing after the same period. CONCLUSIONS: These results indicate that the relative direction of the laser polarization plays an important role in the wound healing process when highly coherent He-Ne laser is used.

Severe nutritional restriction in pregnant rats aggravates hypertension, altered vascular reactivity, and renal development in spontaneously hypertensive rats offspring.

Epidemiologic studies suggest that intrauterine undernutrition plays an important role in the development of arterial hypertension in adulthood. The aim of the current study was to evaluate whether severe nutritional restriction during pregnancy can aggravate hypertension, vascular reactivity changes, and renal development in spontaneously hypertensive rat (SHR) offspring. To investigate the potential existence of gender differences, both male and female offspring of pregnant SHRs on a restricted diet were studied in adulthood. Female pregnant SHRs were fed either normal or 50% of the normal intake diets, during the whole gestational period. Arterial blood pressure and nephron number were determined. Norepinephrine, acetylcholine, and sodium nitroprusside responses in isolated aortic rings from the offspring (male and female, when they reached adulthood) were also evaluated. In the SHR offspring (male and female) the intrauterine undernutrition further increased the blood pressure levels, increased the response to norepinephrine, and decreased the response to acetylcholine, without altering the response to sodium nitroprusside. In addition, it induced a decrease in the number of nephrons in the kidney from adult offspring. In conclusion, fetal undernutrition aggravates hypertension and the endothelial dysfunction along with an impairment of renal development in both male and female SHRs.