The majority of GLUT4 is sequestered in unique intracellular vesicles in the absence of insulin. Upon insulin stimulation GLUT4 vesicles translocate to, and fuse with, the plasma membrane. To determine the effect of GLUT4 content on the distribution and subcellular trafficking of GLUT4 and other vesicle proteins, adipocytes of adipose-specific, GLUT4-deficient (aP2-GLUT4؊/؊) mice and adipose-specific, GLUT4-overexpressing (aP2-GLUT4-Tg) mice were studied. GLUT4 amount was reduced by 80 -95% in aP2-GLUT4؊/؊ adipocytes and increased ϳ10-fold in aP2-GLUT4-Tg adipocytes compared with controls. Insulin-responsive aminopeptidase (IRAP) protein amount was decreased 35% in aP2-GLUT4؊/؊ adipocytes and increased 45% in aP2-GLUT4-Tg adipocytes. VAMP2 protein was also decreased by 60% in aP2-GLUT4؊/؊ adipocytes and increased 2-fold in aP2-GLUT4-Tg adipocytes. IRAP and VAMP2 mRNA levels were unaffected in aP2-GLUT4-Tg, suggesting that overexpression of GLUT4 affects IRAP and VAMP2 protein stability. The amount and subcellular distribution of syntaxin4, SNAP23, Munc-18c, and GLUT1 were unchanged in either aP2-GLUT4؊/؊ or aP2-GLUT4-Tg adipocytes, but transferrin receptor was partially redistributed to the plasma membrane in aP2-GLUT4-Tg adipocytes. Immunogold electron microscopy revealed that overexpression of GLUT4 in adipocytes increased the number of GLUT4 molecules per vesicle nearly 2-fold and the number of GLUT4 and IRAP-containing vesicles per cell 3-fold. In addition, the proportion of cellular GLUT4 and IRAP at the plasma membrane in unstimulated aP2-GLUT4-Tg adipocytes was increased 4-and 2-fold, respectively, suggesting that sequestration of GLUT4 and IRAP is saturable. Our results show that GLUT4 overexpression or deficiency affects the amount of other GLUT4-vesicle proteins including IRAP and VAMP2 and that GLUT4 sequestration is saturable.

Consulting psychiatrists frequently encounter geriatric patients and, given patterns of diagnosis and aftercare, should play a major role in medical staff education and in development of enhanced in-hospital and aftercare services, including psychiatric liaison.

9540 Background: Burnout among physicians is associated with fatigue, exhaustion, and depression, and can result in increased medical errors and sub-standard patient care. We sought to determine rates and predictors of burnout in oncology fellows. Methods: As part of a larger study on fellows' attitudes, education, and experiences in palliative care, we administered the 22 item Maslach Burnout Inventory (MBI) to second year U.S. oncology fellows. The 104 item instrument, modified from a survey of medical students, was revised after field testing and a pilot survey. The MBI measures three domains: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA); higher EE and DP scores and lower PA scores indicate burnout. Bivariate and multivariate analyses were used to find associations between burnout and fellow demographics, attitudes, and educational experiences. To accommodate for multiple testing, p<0.01 was considered statistically significant. Results: The response rate was 63.2% (254 of 402 eligible fellows). Gender, race, and location of medical school (U.S. vs. other) did not differ between respondents and non-respondents. Among respondents, 28.1% reported high EE, 30.0% reported high DP, and 26.8% reported low PA. Over half reported burnout in at least one domain (32.9% in one, 16.5% in two, and 5.5% in all three domains). The following associations were found on multivariate analyses. Fellows who identified as white had higher rates of EE (p=0.0006) while EE was lower in those who: 1) rated their program's overall teaching ‘very good‘ or ‘excellent‘ (p=0.005), 2) felt prepared to address spiritual issues around end-of-life care (p=0.002), and 3) felt prepared to manage their own feelings about illness and dying (p=0.008). Fellows who identified as white (p=0.008) or reported dreading encounters with emotionally distressed family members (p=0.0002) had higher DP. The only factor associated with higher PA scores was agreement that doctors have a responsibility to help patients prepare for death (p<0.0001). Conclusions: Over half of oncology fellows experience at least one domain of burnout. Higher quality teaching within their fellowship program and higher levels of self-assessed preparation to care for patients at the end of life are associated with lower levels of burnout. No significant financial relationships to disclose.