Peroxisome proliferator-activated receptor-alpha agonist treatment in a transgenic model of type 2 diabetes reverses the lipotoxic state and improves glucose homeostasis

Abnormalities in insulin action are the characteristics of type 2 diabetes. Dominant-negative muscle-specific IGF-I receptor (MKR) mice exhibit elevated lipid levels at an early age and eventually develop type 2 diabetes. To evaluate the role of elevated lipids in the progression of the diabetic state, MKR mice were treated with WY14,643, a peroxisome proliferator-activated receptor (PPAR)-alpha agonist. WY14,643 treatment markedly reduced serum fatty acid and triglyceride levels within a few days, as well as muscle triglyceride levels, and subsequently normalized glucose and insulin levels in MKR mice. Hyperinsulinemic-euglycemic clamp analysis showed that WY14,643 treatment enhanced muscle and adipose tissue glucose uptake by improving whole-body insulin sensitivity. Insulin suppression of endogenous glucose production by the liver of MKR mice was also improved. The expression of genes involved in fatty acid oxidation was increased in liver and skeletal muscle, whereas gene expression levels of hepatic gluconeogenic enzymes were decreased in WY14,643-treated MKR mice. WY14,643 treatment also improved the pattern of glucose-stimulated insulin secretion from the perfused pancreata of MKR mice and reduced the beta-cell mass. Taken together, these findings suggest that the reduction in circulating or intracellular lipids by activation of PPAR-alpha improved insulin sensitivity and the diabetic condition of MKR mice.     

Some remarks on failed forceps

Irish Journal of Medical Science (1926-1967) -     

The potential impact of incentives on future blood donation behavior

BACKGROUND: It is important to assess the potential efficacy and safety of offering donation incentives as part of recruitment and retention programs. STUDY DESIGN AND METHODS: In 1995, 7489 allogeneic donors responded to an anonymous mail survey that inquired about demographics, donation history, infectious disease risks, and the potential appeal of incentives. RESULTS: The projected net effect of offering blood credits and medical testing would be to motivate, respectively, 58 percent and 46 percent of donors to return, whereas offering an item of limited value would motivate 20 percent to do so. First-time and younger donors reported more frequently than repeat or older donors that incentives would appeal to them. Donors attracted by cash were 60 percent more likely to have a risk for transfusion-transmissible infections (p = 0.03). Although not statistically significant, the odds of being an at-risk donor were higher among individuals attracted by tickets to events (OR 1.5) and extra time off work (OR 1.2). CONCLUSION: These findings suggest that offering blood credits and (though to a lesser extent) items of limited value could be safe and effective strategies for retaining donors. Although medical tests were found to have broad appeal, studies are needed to identify tests in which donors would be most interested.     

Motivations to donate blood: demographic comparisons

BACKGROUND: Understanding blood donor motivations is crucial to improving effectiveness of donor recruitment and retention programs. STUDY DESIGN AND METHODS: Data from a 1998 survey of 92,581 U.S. blood donors were used to evaluate factors influencing the decision to donate in various demographic groups. Data were weighted to adjust for response and sample design. RESULTS: Of 52,650 respondents, 45,588 gave whole-blood (WB) donations. Among all demographic groups, the major reasons to donate were altruism (75-87%) and awareness of the need for blood (34-43%). Except for first-time donors and those 相似文献