E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.

The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.

Mapping histological and functional maturation of human endocrine pancreas across early postnatal periods.

Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 115 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation.

Blood Pressure Estimation Using Explainable Deep-Learning Models Based on Photoplethysmography.

Background: Due to their invasiveness, arterial lines are not typically used in routine monitoring, despite their superior responsiveness in hemodynamic monitoring and detecting intraoperative hypotension. To address this issue, noninvasive, continuous arterial pressure monitoring is necessary. We developed a deep-learning model that reconstructs continuous mean arterial pressure (MAP) using the photoplethysmograhy (PPG) signal and compared it to the arterial line gold standard.

Heterogeneous endocrine cell composition defines human islet functional phenotypes.

Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers, enabling the integration of multiple data types.

Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice.

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis.