ABSTRACT
To date, no study has examined the value of providing study newsletters in educating and motivating participants taking part in longitudinal intervention studies and reducing attrition in studies. The study team examined perceptions and satisfaction towards study newsletters, and their potential benefits, in a population of older men with prostate cancer participating in two ongoing longitudinal trials. Two study newsletters issues were mailed out 4 months apart to prostate cancer patients participating in a bone health and/or exercise intervention trial. Participants (n = 133) were invited to complete an 18-item custom-designed survey examining perceptions towards and satisfaction with the newsletter, and provide feedback about what makes an ideal study newsletter. Analyses were primarily descriptive. Resources required to produce a study newsletter were also calculated. Of 133 participants, 83 usable surveys were returned (response rate 62.4%). The mean satisfaction rating for the newsletter was 8.5/10 (SD 1.9) (10 = highly satisfied). Seventy eight percent said the newsletter encouraged them to continue to participate in the study, and 93% indicated that providing such study newsletters should be optional (64%) or mandatory (29%). Each newsletter required 31 h of study personnel time (mostly research student) to produce. Study participants were very satisfied with the newsletter and the majority indicated that study newsletters should be a regular practice in all long-term studies and may improve participant retention. Producing a newsletter is a low-cost method of educating participants in longitudinal studies. Its impact on recruitment and retention should be examined in clinical trials.
Subject(s)
Clinical Trials as Topic/psychology , Health Education , Neoplasms/therapy , Patient Participation/psychology , Patient Participation/statistics & numerical data , Periodicals as Topic , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , Male , Middle Aged , Surveys and Questionnaires , Teaching MaterialsABSTRACT
Exocytosis of the hormone glucagon-like peptide 1 (GLP-1) by the intestinal L cell is essential for the incretin effect after nutrient ingestion and is critical for the actions of dipeptidyl peptidase 4 inhibitors that enhance GLP-1 levels in patients with type 2 diabetes. Two-photon microscopy revealed that exocytosis of GLP-1 is biphasic, with a first peak at 1-6 min and a second peak at 7-12 min after stimulation with forskolin. Approximately 75% of the exocytotic events were represented by compound granule fusion, and the remainder were accounted for by full fusion of single granules under basal and stimulated conditions. The core SNARE protein syntaxin-1a (syn1a) was expressed by murine ileal L cells. At the single L-cell level, first-phase forskolin-induced exocytosis was reduced to basal (P < 0.05) and second-phase exocytosis abolished (P < 0.05) by syn1a knockout. L cells from intestinal-epithelial syn1a-deficient mice demonstrated a 63% reduction in forskolin-induced GLP-1 release in vitro (P < 0.001) and a 23% reduction in oral glucose-stimulated GLP-1 secretion (P < 0.05) in association with impairments in glucose-stimulated insulin release (by 60%; P < 0.01) and glucose tolerance (by 20%; P < 0.01). The findings identify an exquisite mechanism of metered secretory output that precisely regulates release of the incretin hormone GLP-1 and hence insulin secretion after a meal.
Subject(s)
Exocytosis/physiology , Gene Expression Regulation/physiology , Glucagon-Like Peptide 1/metabolism , Syntaxin 1/metabolism , Animals , Cells, Cultured , Diabetes Mellitus, Type 2/metabolism , Enteroendocrine Cells/physiology , Female , Glucagon-Like Peptide 1/genetics , Glucose/metabolism , Ileum/cytology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Obesity/metabolism , Syntaxin 1/geneticsABSTRACT
Obesity is associated with systemic inflammation and elevated levels of TNFα, leading to impaired glucose tolerance. In humans, obesity is also associated with reduced nutrient-stimulated secretion of the intestinal incretin hormone, glucagon-like peptide-1 (GLP-1). We hypothesized that TNFα plays a direct role in the impairment of GLP-1 secretion from the enteroendocrine L-cell and that blocking TNFα can restore both GLP-1 secretion and glucose homeostasis. Expression of the TNFα receptor subytpe-1 was detected in the human NCI-H716 and murine GLUTag L-cell models and in mouse ileal sections. Although TNFα acutely increased GLP-1 release from NCI-H716 cells (P < .05-.001), preincubation with TNFα for 24 hours reduced proglucagon mRNA (P < .05) and GLP-1 cellular (P < .05) levels without affecting cell viability. Furthermore, both NCI-H716 and GLUTag cells pretreated with TNFα for 24 hours no longer responded to known GLP-1 secretagogues, an effect that was reversed by coincubation with the Nuclear Factor Kappa B inhibitor, 5-aminosalicylic acid, in the NCI-H716 cells. Mice given a high-fat diet (HFD) for 12 weeks developed impaired glucose tolerance, hyperinsulinemia, and increased TNFα mRNA expression in fat and ileal tissue. Hyperglycemia and hyperinsulinemia were reduced in HFD mice treated with the anti-TNFα biological, etanercept, for 2 weeks. In primary intestinal cultures from these animals, HFD control mice had impaired GLP-1 secretion, and this was not observed in the HFD etanercept-derived cultures (P < .05). In conclusion, chronic exposure to TNFα directly impairs GLP-1 secretion at the level of the intestinal L-cell, an effect that is reversed by anti-TNFα therapy in association with improved glucose tolerance.
