Insulin resistance and β-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and β-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of β-cell cytoplasmic free Ca 2+ concentration ([Ca 2+ ] i ) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca 2+
Acoustic stimulation gates mechanically sensitive ion channels in cochlear sensory hair cells. Even in the absence of sound, a fraction of these channels remains open, forming a conductance between hair cells and the adjacent fluid space, scala media. Restoring the lost endogenous polarization of scala media in an in vitro preparation of the whole cochlea depolarizes the hair cell soma. Using both digital laser interferometry and time-resolved confocal imaging, we show that this causes a structural refinement within the organ of Corti that is dependent on the somatic electromotility of the outer hair cells (OHCs). Specifically, the inner part of the reticular lamina up to the second row of OHCs is pulled toward the basilar membrane, whereas the outer part (third row of OHCs and the Hensen's cells) unexpectedly moves in the opposite direction. A similar differentiated response pattern is observed for sound-evoked vibrations: restoration of the endogenous polarization decreases vibrations of the inner part of the reticular lamina and results in up to a 10-fold increase of vibrations of the outer part. We conclude that the endogenous polarization of scala media affects the function of the hearing organ by altering its geometry, mechanical and electrical properties.
Little is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca 2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.