A B S T R A C T The pathologies of diabetic micro-and macroangiopathy are different, suggesting that diabetes affects these two types of vascular tissue in a dissimilar manner. We have compared insulin receptors and the effects of insulin on cultured endothelium from calf retinal capillaries and aorta, and the vascular supporting cells, retinal pericytes, and aortic smooth muscle cells. '251-insulin binds to high affinity insulin receptors on all four cell types. Receptor concentrations were similar except for aortic smooth muscle cells, which have 10-fold fewer receptors than the other cell types. Insulin at a concentration of 10 ng/ ml stimulated ['4C]glucose incorporation into glycogen in retinal endothelial cells and pericytes and aortic smooth muscle cells, but had no effect on aortic endothelium. Insulin over a concentration range of 10 ng/ml-10 ,ug/ml, stimulated [3H]thymidine incorporation into the DNA of retinal pericytes, and endothelial cells and aortic smooth muscle cells but had no effect on aortic endothelial cells. These data suggested that a differential response to insulin may exist between endothelium of micro-and macrovasculature, and suggest that retinal capillary endothelium and retinal pericytes are both very insulin-sensitive tissues.

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BACKGROUND:Postoperative sepsis is one of the main causes of death after major abdominal surgery; however, the immunologic factors contributing to the development of sepsis are not completely understood. In this study, we evaluated gene expression in patients who developed postoperative sepsis and in patients with an uncomplicated postoperative course.

Purpose. The patient’s perspective is becoming increasingly important in clinical and policy decisions. This study examined atrial fibrillation (AF) patient preferences for different characteristics of nonvitamin K antagonist oral anticoagulants (NOACs). Methods. A discrete choice experiment (DCE) addressing AF patients treated with NOACs in France, Germany, and the United Kingdom was conducted. The DCE included the following attributes: frequency of administration (once/twice daily), size of tablet/capsule (6–9 mm/20 mm), meal-related intake (intake with food required/independent), and distance to treating physician (1 km/10 km). Preferences were analyzed based on a conditional logit regression model. Results. In total, 758 patients (males: 57.3%; mean age: 71.4 years) with an average disease duration of 5.5 years were included (apixaban/dabigatran/edoxaban/rivaroxaban: 34.0%/14.5%/6.6%/44.9%, respectively). Patients preferred NOAC treatment options characterized by once-daily dosing regimens (42.8%; p<0.001), shorter distance to treating physicians (25.0%; p<0.001), a small-sized tablet (21.5%; p<0.001), and intake independent of food (10.6%; p<0.001). Conclusions. Patients primarily prefer a once-daily NOAC regimen. Individual preferences should be considered for the treatment of AF patients as this may result in improved treatment adherence and consequently better effectiveness and safety in routine clinical practice.

Insulin binding and processing was studied in monolayer cultures of bovine aortic endothelial cells. Specific 125I-insulin binding was both time and temperature dependent. Maximum binding at 37 degrees C occurred at 90 min, and was 3.8%/mg protein and, at 15 degrees C, 7%/mg protein at 4 h. 125I-insulin was crosslinked to its receptor using disuccinimidyl suberate (DSS), and the structure of the receptor complex was identified by SDS-polyacrylamide gel electrophoresis and autoradiography; a major band with Mr = 145,000 was identified, which corresponds to the alpha-subunit of the insulin receptor reported in other tissues. Receptor-bound insulin was internalized, and both the rate and the amount of internalization were temperature dependent. The rate of internalization was slowest at 4 degrees C, and fastest at 37 degrees C, and the maximum amount of 125I-insulin internalized in 120 min was 16% at 4 degrees C, 45% at 15 degrees C, and 81% at 37 degrees C. Despite the high rate of internalization, endothelial cells do not appear to degrade insulin significantly, as determined by gel chromatography and TCA solubility (7% at 4 h) of media-associated radioactivity. In addition, the majority of internalized insulin (75%) was released by 60 min, largely as intact insulin. Chloroquine treatment at high concentration did not exert any major effect on insulin binding or degradation within the first 60 min, but thereafter produced a marked increase in cell-associated radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)