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Several genetically encoded sensors have been developed to study live cell NADPH/NADP + dynamics, but their use has been predominantly in vitro. Here, we developed an in vivo assay using the Apollo-NADP + sensor and microfluidic devices to measure endogenous NADPH/NADP + dynamics in the pancreatic β cells of live zebrafish embryos. Flux through the pentose phosphate pathway, the main source of NADPH in many cell types, has been reported to be low in β cells. Thus, it is unclear how these cells compensate to meet NADPH demands. Using our assay, we show that pyruvate cycling is the main source of NADP + reduction in β cells, with contributions from folate cycling after acute electrical activation. INS1E β cells also showed a stress-induced increase in folate cycling and further suggested that this cycling requires both increased glycolytic intermediates and cytosolic NAD + . Overall, we show in vivo application of the Apollo-NADP + sensor and reveal that β cells are capable of adapting NADPH/NADP + redox during stress.

Human genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in NEMP1 ( nuclear envelope membrane protein 1 ) with early menopause; however, it is unclear whether NEMP1 has any role in fertility. We show that whole-animal loss of NEMP1 homologs in Drosophila , Caenorhabditis elegans , zebrafish, and mice leads to sterility or early loss of fertility. Loss of Nemp leads to nuclear shaping defects, most prominently in the germ line. Biochemical, biophysical, and genetic studies reveal that NEMP proteins support the mechanical stiffness of the germline nuclear envelope via formation of a NEMP-EMERIN complex. These data indicate that the germline nuclear envelope has specialized mechanical properties and that NEMP proteins play essential and conserved roles in fertility., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)