Exenatide Improves Glucose Homeostasis and Prolongs Survival in a Murine Model of Dilated Cardiomyopathy

There is growing awareness of secondary insulin resistance and alterations in myocardial glucose utilization in congestive heart failure. Whether therapies that directly target these changes would be beneficial is unclear. We previously demonstrated that acute blockade of the insulin responsive facilitative glucose transporter GLUT4 precipitates acute decompensated heart failure in mice with advanced dilated cardiomyopathy. Our current objective was to determine whether pharmacologic enhancement of insulin sensitivity and myocardial glucose uptake preserves cardiac function and survival in the setting of primary heart failure.The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life. TG9 mice develop congestive heart failure and secondary insulin resistance in a highly predictable manner with death by 12 weeks of age. Glucose homeostasis was assessed by measuring glucose tolerance at 8 and 10 weeks and tissue 2-deoxyglucose uptake at 75 days. Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice. Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals. Total myocardial GLUT1 levels were not different between groups. Exenatide also abrogated the detrimental effect of the GLUT4 antagonist ritonavir on survival in TG9 mice.In heart failure secondary insulin resistance is maladaptive and myocardial glucose uptake is suboptimal. An incretin-based therapy, which addresses these changes, appears beneficial

The Role of Sociocultural Influences on Symptoms of Muscle Dysmorphia and Eating Disorders in Men, and the Mediating Effects of Perfectionism

This study examined the mediating role of self-oriented and socially prescribed perfectionism in the relationship between sociocultural influences (i.e., media, peer, and teasing) and symptoms of muscle dysmorphia (MD) and eating disorders (ED). A nonclinical sample of males (N = 158, Mage = 26.94, SD = 5.50) completed measures of perfectionism, MD, body dissatisfaction, drive for thinness, and bulimia. Susceptibility to appearance-based messages from the media, their peers, and family was also measured. Analyses confirmed the partial mediating role of self-oriented perfectionism only for drive for thinness. In contrast, socially prescribed perfectionism was found to be a partial mediator between all three sociocultural variables and measures of both MD and ED; except for those between peer influence and body dissatisfaction, and teasing and bulimia symptomatology. These two relationships were fully mediated by socially prescribed perfectionism. Results suggest that vulnerability to MD and ED depend on pre-existing perfectionistic attitudes, particularly that of socially prescribed perfectionism