Immunotherapy With Low-Dose IL-2/CD25 Prevents ß-Cell Dysfunction and Dysglycemia in Prediabetic NOD Mice.

Low-dose IL-2 is a promising immunotherapy in clinical trials for treating type 1 diabetes. A new IL-2 analog, IL-2/CD25 fusion protein, has been shown to more efficiently delay or prevent diabetes in NOD mice by expanding the population of activated regulatory T cells. This therapy is intended for use before clinical diagnosis, in the early stages of type 1 diabetes progression. During this prediabetic period, there is a chronic decline in ß-cell function that has long-term implications for disease pathogenesis. Yet, to date, the effects of IL-2/CD25 on ß-cell function have not been evaluated. In this study, we treated prediabetic NOD mice with low-dose mouse IL-2/CD25 over 5 weeks and determined its impact on ß-cell function. This treatment limited the progressive impairment of glucose tolerance and insulin secretion typical of the later stages of prediabetes. Intracellular Ca2+ responses to glucose in ß-cells became more robust and synchronous, indicating that changing the local immune cell infiltrate with IL-2/CD25 preserved ß-cell function even after treatment cessation. Our study thus provides mechanistic insight and serves as a steppingstone for future research using low-dose IL-2/CD25 immunotherapy in patients. ARTICLE HIGHLIGHTS: Immunotherapies such as IL-2/CD25 are known to prevent or delay diabetes. However, their impact on individual ß-cell function is not yet understood. Female NOD mice progress from stage 1 to 2 pre-type 1 diabetes between 12 and 17 weeks. Treatment with mouse IL-2 (mIL-2)/CD25 prevents this progression even after treatment cessation. Individual ß-cell function (measured via intracellular Ca2+ responses to glucose) declines during the pathogenesis of type 1 diabetes. Treatment with mIL-2/CD25 therapy limits ß-cell dysfunction, and function continues to improve after treatment cessation. Insulin secretion is improved with mIL-2/CD25 therapy.

An Update on the Use of Wearable Devices in Men's Health.

Men's health represents an often-overlooked aspect of public health. Men have higher mortality rates worldwide and are more negatively affected by chronic conditions such as obesity and heart disease, as well as addiction to alcohol and tobacco. Men also have health issues such as prostate cancer and male sexual dysfunction which only affect them. Because of the skewed burden of morbidity and mortality on men, it is imperative from a public health perspective to make a concerted effort to specifically improve men's health. The use of wearable devices in medical practice presents a novel avenue to invest in men's health in a safe, easily scalable, and economic fashion. Wearable devices are now ubiquitous in society, and their use in the healthcare setting is only increasing with time. There are commercially available devices such as smart watches which are available to lay people and healthcare professionals alike to improve overall health and wellness, and there are also purpose-built wearable devices which are used to track or treat a specific disease. In our review of the literature, we found that while research in the field of wearable devices is still in its early stages, there is ample evidence that wearable devices can greatly improve men's health in the long-term.

Stress-induced dissociations between intracellular calcium signaling and insulin secretion in pancreatic islets.

In healthy pancreatic islets, glucose-stimulated changes in intracellular calcium ([Ca(2+)]i) provide a reasonable reflection of the patterns and relative amounts of insulin secretion. We report that [Ca(2+)]i in islets under stress, however, dissociates with insulin release in different ways for different stressors. Islets were exposed for 48h to a variety of stressors: cytokines (low-grade inflammation), 28mM glucose (28G, glucotoxicity), free fatty acids (FFAs, lipotoxicity), thapsigargin (ER stress), or rotenone (mitochondrial stress). We then measured [Ca(2+)]i and insulin release in parallel studies. Islets exposed to all stressors except rotenone displayed significantly elevated [Ca(2+)]i in low glucose, however, increased insulin secretion was only observed for 28G due to increased nifedipine-sensitive calcium-channel flux. Following 3-11mM glucose stimulation, all stressors substantially reduced the peak glucose-stimulated [Ca(2+)]i response (first phase). Thapsigargin and cytokines also substantially impacted aspects of calcium influx and ER calcium handling. Stressors did not significantly impact insulin secretion in 11mM glucose for any stressor, although FFAs showed a borderline reduction, which contributed to a significant decrease in the stimulation index (11:3mM glucose) observed for FFAs and also for 28G. We also clamped [Ca(2+)]i using 30mM KCl+250µM diazoxide to test the amplifying pathway. Only rotenone-treated islets showed a robust increase in 3-11mM glucose-stimulated insulin secretion under clamped conditions, suggesting that low-level mitochondrial stress might activate the metabolic amplifying pathway. We conclude that different stressors dissociate [Ca(2+)]i from insulin secretion differently: ER stressors (thapsigargin, cytokines) primarily affect [Ca(2+)]i but not conventional insulin secretion and 'metabolic' stressors (FFAs, 28G, rotenone) impacted insulin secretion.