Leveraging digital assets: lessons from a 14-year-old isotope tracer course for professional scientists.

The COVID-19 pandemic and subsequent policies (e.g., social distancing, travel restrictions) challenged both organizers for and attendees of programs typically held in person. Many scientific training programs quickly adapted to virtual formats by incorporating digital assets developed for virtual learning and remote social engagement. At the outset, the value of continuing digital elements with future in-person events was unclear. To examine how virtual resources supported heterogeneous professional training programs, we reviewed survey data for a 14-year-old training program for scientific professionals titled "Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis." We found a positive relationship between survey satisfaction and the postpandemic in-person program that included digital assets held in 2022 compared to prepandemic in-person programs. To better understand the postpandemic program satisfaction, we assessed the 2021 virtual course format and survey data. We found that although there was a desire to return to in-person programs, the digital assets and approaches were valued. In examining the individual programmatic elements in the 2022 in-person course, there was better "value and understandability" of lectures over previous in-person years. These findings highlight how incorporating new digital engagement strategies for professional development benefits even the most established programs in supporting heterogeneous learners.NEW & NOTEWORTHY We examined impact of leveraging digital assets to support virtual engagement for an in-person program. Using survey data of a 14-year-old program for scientific professionals, we compared pre- and postpandemic in-person programs. Through incorporating digital assets, we found increased survey satisfaction compared to prepandemic in-person programs. These findings highlight how incorporating new digital engagement strategies benefits even the most successful professional development programs.

Insulin at the intersection of thermoregulation and glucose homeostasis.

Mammals are protected from changes in environmental temperature by altering energetic processes that modify heat production. Insulin is the dominant stimulus of glucose uptake and metabolism, which are fundamental for thermogenic processes. The purpose of this work was to determine the interaction of ambient temperature induced changes in energy expenditure (EE) on the insulin sensitivity of glucose fluxes. Short-term and adaptive responses to thermoneutral temperature (TN, ∼28 °C) and room (laboratory) temperature (RT, ∼22 °C) were studied in mice. This range of temperature does not cause detectable changes in circulating catecholamines or shivering and postabsorptive glucose homeostasis is maintained. We tested the hypothesis that a decrease in EE that occurs with TN causes insulin resistance and that this reduction in insulin action and EE is reversed upon short term (<12h) transition to RT. Insulin-stimulated glucose disposal (Rd) and tissue-specific glucose metabolic index were assessed combining isotopic tracers with hyperinsulinemic-euglycemic clamps. EE and insulin-stimulated Rd are both decreased (∼50%) in TN-adapted vs RT-adapted mice. When RT-adapted mice are switched to TN, EE rapidly decreases and Rd is reduced by ∼50%. TN-adapted mice switched to RT exhibit a rapid increase in EE, but whole-body insulin-stimulated Rd remains at the low rates of TN-adapted mice. In contrast, whole body glycolytic flux rose with EE. This higher EE occurs without increasing glucose uptake from the blood, but rather by diverting glucose from glucose storage to glycolysis. In addition to adaptations in insulin action, 'insulin-independent' glucose uptake in brown fat is exquisitely sensitive to thermoregulation. These results show that insulin action adjusts to non-stressful changes in ambient temperature to contribute to the support of body temperature homeostasis without compromising glucose homeostasis.

Repression of latent NF-κB enhancers by PDX1 regulates ß cell functional heterogeneity.

Interactions between lineage-determining and activity-dependent transcription factors determine single-cell identity and function within multicellular tissues through incompletely known mechanisms. By assembling a single-cell atlas of chromatin state within human islets, we identified ß cell subtypes governed by either high or low activity of the lineage-determining factor pancreatic duodenal homeobox-1 (PDX1). ß cells with reduced PDX1 activity displayed increased chromatin accessibility at latent nuclear factor κB (NF-κB) enhancers. Pdx1 hypomorphic mice exhibited de-repression of NF-κB and impaired glucose tolerance at night. Three-dimensional analyses in tandem with chromatin immunoprecipitation (ChIP) sequencing revealed that PDX1 silences NF-κB at circadian and inflammatory enhancers through long-range chromatin contacts involving SIN3A. Conversely, Bmal1 ablation in ß cells disrupted genome-wide PDX1 and NF-κB DNA binding. Finally, antagonizing the interleukin (IL)-1ß receptor, an NF-κB target, improved insulin secretion in Pdx1 hypomorphic islets. Our studies reveal functional subtypes of single ß cells defined by a gradient in PDX1 activity and identify NF-κB as a target for insulinotropic therapy.