Insulin-and glyburide-stimulated changes in cytosolic free calcium concentrations (QCa2+Ii) were studied in gluteal adipocytes obtained from six obese women (139±3% ideal body wt) and six healthy, normal weight age-and sex-matched controls. Biopsies were performed after an overnight fast and twice (at 3 and 6 h) during an insulin infusion (40 mU/m2 per min) (euglycemic clamp). In adipocytes obtained from normal subjects before insulin infusion, insulin (10 ng/ml) increased [Ca2+ji from 146±26 nM to 391±66 nM. Similar increases were evoked by 2 tiM glyburide (329±41 nM). After 3 h of insulin infusion, basal ICa2+ii rose to 234±21 nM, but the responses to insulin and glyburide were completely abolished. In vitro insulin-stimulated 2-deoxyglucose uptake was reduced by insulin and glucose infusion (25% stimulation before infusion, 5.4% at 3 h, and 0.85% at 6 h of infusion). Rat adipocytes were preincubated with 1-10 mM glucose and 10 ng/ml insulin for 24 h. Measurements of 2-deoxyglucose uptake demonstrated insulin resistance in these cells.Under these experimental conditions, increased levels of [Ca2+Ii that were no longer responsive to insulin were demonstrated. Verapamil in the preincubation medium prevented the development of insulin resistance.

Two studies were conducted to demonstrate that maladaptive aspects of high and low Openness to Experience were related to characterological impairment and that this aspect of personality may define a new domain of personality dysfunction. The 55-item Experiential Permeability Inventory (EPI; containing 4 scales) was developed and demonstrated to have acceptable psychometric properties. Evidence of convergent, discriminant, and incremental validity was provided. These studies provide a methodological framework for identifying and developing aspects of personality dysfunction that can expand the comprehensiveness of the current set of Axis II disorders. Theoretical implications of the EPI are discussed.

In this study of men with ED, sildenafil produced substantial improvements in self-esteem, confidence and relationship satisfaction as measured by SEAR scores, which showed moderate to high positive correlations with IIEF scores.

We have recently provided evidence that elevated levels of cytosolic free Ca2+ ([Ca2+]i) decreased insulin-stimulated glucose uptake in isolated rat adipocytes. To investigate the mechanism of Ca2+ action, we examined the effects of elevated levels of [Ca2+]i on insulin binding, autophosphorylation, and tyrosine kinase activity (TKA) of insulin receptors as well as basal and insulin-stimulated cellular distribution of glucose transporters. The latter was assessed by cytochalasin-B binding to plasma membrane and cytosolic fractions. Elevated concentrations of [Ca2+]i were maintained by incubating adipocytes with a depolarizing concentration of K+ (40 mM). Basal nonstimulated glucose uptake was not altered by increased levels of [Ca2+]i. Adipocytes with higher [Ca2+]i (220 +/- 15 nM) showed 30% reduction in insulin-stimulated 2-deoxyglucose uptake compared with control cells ([Ca2+]i, 140 +/- 18 nM). Moreover, adipocytes with higher levels of [Ca2+]i demonstrated an approximately 10% reduction in autophosphorylation and TKA of insulin receptors without a change in insulin binding. Both basal and insulin-stimulated distributions of glucose transporters were unaffected by sustained levels of [Ca2+]i. The effects of elevated [Ca2+]i were not mimicked by protein kinase-C activation. These observations suggest that 1) elevated or sustained levels of [Ca2+]i impair insulin-stimulated glucose uptake; and 2) Ca2+-induced impairment appears to reside at the postbinding steps of insulin action and probably interferes with the TKA of insulin receptors and the intrinsic activity of glucose transporters.