The antidiabetic drug Metformin causes weight loss in both diabetic and non-diabetic individuals. Metformin treatment is also associated with lower circulating levels of the orexigenic hormone ghrelin. To test whether Metformin directly affects ghrelin cells, rat primary stomach cells were treated with Metformin and the levels of ghrelin secretion, proghrelin gene expression and activation of adenosine monophosphate-activated protein kinase (AMPK) were examined. Metformin significantly reduced ghrelin secretion and proghrelin mRNA production and both these effects were blocked by co-incubation with the AMPK inhibitor compound C. Furthermore, the AMPK activator 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) significantly inhibited ghrelin secretion. Additionally, ghrelin cells were shown to express AMPK. Finally, Metformin treatment caused a significant increase in the level of phosphorylated (active) AMPK. Our results show that Metformin directly inhibits stomach ghrelin production and secretion through AMPK. This reduction in ghrelin secretion may be one of the key components in Metformin's mechanism of weight loss.
BACKGROUND: Muscle weakness is an important systemic consequence in adults with cystic fibrosis, but it can be challenging to evaluate clinically. This study examined the validity of lowerextremity functional tests to assess quadriceps muscle strength and muscle power. METHODS: The subjects underwent 4 functional tests: 30-s sit-to-stand test, stair-climb power test, vertical jump height, and triple hop distance. Quadriceps muscle strength and power were tested by using a dynamometer (the accepted standard). Quadriceps strength was measured from 5 maximum voluntary isometric contractions to obtain peak torque. Quadriceps power was evaluated from the peak power and peak velocity attained during isotonic contractions of the quadriceps at a preset load of 20% of the peak torque. Pearson correlations were used to determine associations between functional tests and accepted measures of quadriceps strength and power. RESULTS: Fifteen adults with cystic fibrosis (9 males; mean ؎ SD age, 32 ؎ 13 y; mean ؎ SD FEV 1 % predicted, 73 ؎ 19) completed the study. The stair-climb power test had the strongest correlations with peak torque (r ؍ 0.84, P < .001) and power (r ؍ 0.65, P ؍ .009). Vertical jump height was moderately correlated with quadriceps strength (r ؍ 0.62, P ؍ .014) and quadriceps peak power (r ؍ 0.51, P ؍ .048). Similarly, triple hop distance had moderate correlations with quadriceps strength (r ؍ 0.78, P ؍ .001) and peak power (r ؍ 0.57, P ؍ .026). The sit-to-stand test was only associated with quadriceps strength (r ؍ 0.55, P ؍ .034). CONCLUSIONS: Functional tests can be applied clinically to measure leg muscle strength and power, with the stair-climb power test having the strongest associations with the standard measures. The utility of using functional tests to evaluate longitudinal changes in muscle function and its association with clinical outcomes should be examined in cystic fibrosis.
Objective
To assess the effect the Pre-clerkship Residency Exploration Program (PREP) had on student career interest and improving understanding of physical medicine and rehabilitation (PMR).
Design
During a 2-week program, students were exposed to a PMR elective, workshop, career presentation, and panel discussion with PMR residents. Interest and understanding were assessed using pre- and postprogram questionnaires.
Setting
PREP was held at a Canadian medical school during the summer between the second and third years of undergraduate medical training.
Participants
Second-year medical student participants (N=40) (26 women and 14 men, aged 20 to >30 y) were randomly selected from 74 applicants at a Canadian medical school.
Interventions
Of the 40 program participants, 20 participated in a PMR elective and specialty-specific workshop. The full cohort of 40 participants participated in the PMR career presentation and PMR resident panel discussion.
Main Outcome Measure
Primary outcome measure was an increase in understanding of the PMR specialty.
Results
Understanding of the roles and responsibilities of physiatrists increased significantly, with larger trends in those with greater exposure time. After PREP, comfort level in common PMR procedures also significantly increased. Higher exposure time was correlated with an increased top 3 career selection. Student interest in PMR did not significantly change after the program.
Conclusion
Although no statistically significant effects were found from the 2-week PREP in this population in terms of career choice, benefits were found in the participants comfort with PMR procedures and understanding the roles and responsibilities of physiatrists. A brief exposure as part of a 2-week summer elective is beneficial for career decision planning and may be feasible to implement in medical curricula.
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