Macrophage dysfunction is a likely mechanism underlying common diabetic complications such as increased susceptibility to infection, accelerated atherosclerosis, and disturbed wound healing. There are no available studies on the function of tissue macrophages in diabetes in humans. We have therefore studied peritoneal macrophages from diabetic type 2-like db/db mice. We found that the release of tumor necrosis factor-␣ and interleukin-1␤ from lipopolysaccharide plus interferon-␥-stimulated macrophages and vascular endothelial growth factor from both stimulated and nonstimulated macrophages was significantly reduced in diabetic animals compared with nondiabetic controls. Nitric oxide production from the stimulated db/db macrophages was significantly higher than that in the db/+ cultures, whereas there was no difference in their ability to generate reactive oxygen species. When studied both at light and electron microscopic levels, macrophages in diabetic animals had an altered morphological appearance compared with those of normal controls. We conclude that the function and morphology of the macrophages are disturbed in db/db mice and that this disturbance is related to the mechanisms underlying common inflammatory and degenerative manifestations in diabetes.

Background: The role of serum uric acid as an independent predictor of cardiovascular disease and death is uncertain in the general population. Adjustments for additional cardiovascular risk factors have not been consistent. We examined the association of serum uric acid with all-cause mortality, ischemic stroke and myocardial infarction in a prospective population based study, with several traditional and non-traditional risk factors for cardiovascular disease included in the model. Methods: A population-based prospective cohort study was performed among 2696 men and 3004 women. Endpoints were all-cause mortality after 15 years, and fatal or non-fatal myocardial infarction (MI) and ischemic stroke after 12 years. Results: 1433 deaths, 659 MIs and 430 ischemic strokes occurred during follow-up. Fully adjusted Cox regression analyses showed that per 1 SD (87 μmol/L) increase in serum uric acid level, the risk of all-cause mortality increased in both genders (hazard ratios, HR men; 1.11, 95% CI 1.02-1.20, women; 1.16, 1.05-1.29). HRs and 95% CI for stroke were 1.31, 1.14-1.50 in men, 1.13, 0.94-1.36 in women, and 1.22 (1.09, 1.35) in the overall population. No independent associations were observed with MI.

BackgroundHyperuricemia can lead to gout, and may be a risk factor for cardiovascular events, hypertension, diabetes and renal disease. There is well-known link between gout and habitual intake of meat and seafood, however the association between hyperuricemia and micro-and macro-nutrient intake has not been established.MethodsWe studied associations between intakes of food categories, macro-and micronutrients and serum uric acid (SUA) levels in two cross-sectional surveys of Caucasian adults deriving from different food traditions: Australian Diabetes, Obesity and Lifestyle Study 1999/00 (n=9734, age 25–91) and Tromsø Study 4 1994/95 (n = 3031, age 25–69). Dietary intake was calculated from self-administered Food Frequency Questionnaires. In some analyses we stratified according to abdominal obesity status and gender.ResultsIn both cohorts, lower levels of SUA were found in subjects with higher consumption of carbohydrates, calcium and vitamin B2, while higher fat intake was associated with higher SUA, after adjustment for age, body mass index, estimated glomerular filtration rate, physical activity, total energy intake, use of diuretics, presence of hypertension, diabetes and gout. Among individual food items, high consumption of dairy products, high-fibre bread, cereals and fruits were associated with lower SUA in most subject groups while consumption of meat, eggs, beer and spirits, but not wine, with elevated levels.ConclusionsHealthy food choices with high intake of carbohydrates, dairy products, fiber and micronutrient-rich foods, and limited intake of fat, beer and spirits, might be recommended to prevent high SUA. Dietary factors seem to have qualitatively similar impact on SUA in obese and non-obese men and women from Australia and Norway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-015-0032-1) contains supplementary material, which is available to authorized users.

Fenestrations are transcellular pores in endothelial cells that facilitate transfer of substrates between blood and the extravascular compartment. In order to understand the regulation and formation of fenestrations, the relationship between membrane rafts and fenestrations was investigated in liver sinusoidal endothelial cells where fenestrations are grouped into sieve plates. Three dimensional structured illumination microscopy, scanning electron microscopy, internal reflectance fluorescence microscopy and two-photon fluorescence microscopy were used to study liver sinusoidal endothelial cells isolated from mice. There was an inverse distribution between sieve plates and membrane rafts visualized by structured illumination microscopy and the fluorescent raft stain, Bodipy FL C5 ganglioside GM1. 7-ketocholesterol and/or cytochalasin D increased both fenestrations and lipid-disordered membrane, while Triton X-100 decreased both fenestrations and lipid-disordered membrane. The effects of cytochalasin D on fenestrations were abrogated by co-administration of Triton X-100, suggesting that actin disruption increases fenestrations by its effects on membrane rafts. Vascular endothelial growth factor (VEGF) depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered regions of endothelial cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished.