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  1. Article ; Online: Paracrine Signaling by Pancreatic Islet Cilia.

    Adamson, Samantha E / Hughes, Jing W

    Current opinion in endocrine and metabolic research

    2024  Volume 35

    Abstract: The primary cilium is a sensory and signaling organelle present on most pancreatic islet endocrine cells, where it receives and interprets a wide range of intra-islet chemical cues including hormones, peptides, and neurotransmitters. The ciliary membrane ...

    Abstract The primary cilium is a sensory and signaling organelle present on most pancreatic islet endocrine cells, where it receives and interprets a wide range of intra-islet chemical cues including hormones, peptides, and neurotransmitters. The ciliary membrane possesses a molecular composition distinct from the plasma membrane, with enrichment of signaling mediators including G protein-coupled receptors (GPCRs), tyrosine kinase family receptors, membrane transporters and others. When activated, these membrane proteins interact with ion channels and adenylyl cyclases to trigger local Ca
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Journal Article
    ISSN 2451-9650
    ISSN (online) 2451-9650
    DOI 10.1016/j.coemr.2024.100505
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Rediscovering Primary Cilia in Pancreatic Islets.

    Lee, Eun Young / Hughes, Jing W

    Diabetes & metabolism journal

    2023  Volume 47, Issue 4, Page(s) 454–469

    Abstract: Primary cilia are microtubule-based sensory and signaling organelles on the surfaces of most eukaryotic cells. Despite their early description by microscopy studies, islet cilia had not been examined in the functional context until recent decades. In ... ...

    Abstract Primary cilia are microtubule-based sensory and signaling organelles on the surfaces of most eukaryotic cells. Despite their early description by microscopy studies, islet cilia had not been examined in the functional context until recent decades. In pancreatic islets as in other tissues, primary cilia facilitate crucial developmental and signaling pathways in response to extracellular stimuli. Many human developmental and genetic disorders are associated with ciliary dysfunction, some manifesting as obesity and diabetes. Understanding the basis for metabolic diseases in human ciliopathies has been aided by close examination of cilia action in pancreatic islets at cellular and molecular levels. In this article, we review the evidence for ciliary expression on islet cells, known roles of cilia in pancreas development and islet hormone secretion, and summarize metabolic manifestations of human ciliopathy syndromes. We discuss emerging data on primary cilia regulation of islet cell signaling and the structural basis of cilia-mediated cell crosstalk, and offer our interpretation on the role of cilia in glucose homeostasis and human diseases.
    MeSH term(s) Humans ; Cilia/genetics ; Cilia/metabolism ; Islets of Langerhans ; Diabetes Mellitus/metabolism ; Signal Transduction ; Metabolic Diseases/metabolism
    Language English
    Publishing date 2023-04-28
    Publishing country Korea (South)
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2602402-0
    ISSN 2233-6087 ; 2233-6087
    ISSN (online) 2233-6087
    ISSN 2233-6087
    DOI 10.4093/dmj.2022.0442
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Immuno-Scanning Electron Microscopy of Islet Primary Cilia.

    Sviben, Sanja / Polino, Alexander J / Melena, Isabella / Hughes, Jing W

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The definitive demonstration of protein localization on primary cilia has been a challenge for cilia biologists. Primary cilia are solitary thread-like projections that contain specialized protein composition, but as the ciliary structure overlays the ... ...

    Abstract The definitive demonstration of protein localization on primary cilia has been a challenge for cilia biologists. Primary cilia are solitary thread-like projections that contain specialized protein composition, but as the ciliary structure overlays the cell membrane and other cell parts, the identity of ciliary proteins are difficult to ascertain by conventional imaging approaches like immunofluorescence microscopy. Surface scanning electron microscopy combined with immuno-labeling (immuno-SEM) bypasses some of these indeterminacies by unambiguously showing protein expression in the context of the 3D ultrastructure of the cilium. Here we apply immuno-SEM to specifically identify proteins on the primary cilia of mouse and human pancreatic islets, including post-translationally modified tubulin, intraflagellar transport (IFT) 88, the small GTPase Arl13b, as well as subunits of axonemal dynein. Key parameters in sample preparation, immuno-labeling, and imaging acquisition are discussed to facilitate similar studies by others in the cilia research community.
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.16.580695
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Cilia Action in Islets: Lessons From Mouse Models.

    Cho, Jung Hoon / Hughes, Jing W

    Frontiers in endocrinology

    2022  Volume 13, Page(s) 922983

    Abstract: Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia ...

    Abstract Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia function contributes to the development of diabetes. The complex role of islet primary cilia has been examined using genetic deletion targeting various components of cilia. In this review, we summarize experimental models for the study of islet cilia and current understanding of mechanisms of cilia regulation of islet hormone secretion. Consensus from these studies shows that pancreatic cilia perturbation can cause both endocrine and exocrine defects that are relevant to human disease. We discuss future research directions that would further elucidate cilia action in distinct groups of islet cells, including paracrine and juxtacrine regulation, GPCR signaling, and endocrine-exocrine crosstalk.
    MeSH term(s) Animals ; Cilia/metabolism ; Diabetes Mellitus/metabolism ; Disease Models, Animal ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/metabolism ; Mice ; Pancreas/physiology
    Language English
    Publishing date 2022-06-23
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.922983
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Beta cell primary cilia mediate somatostatin responsiveness via SSTR3.

    Adamson, Samantha E / Li, Zipeng A / Hughes, Jing W

    Islets

    2023  Volume 15, Issue 1, Page(s) 2252855

    Abstract: Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address ... ...

    Abstract Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address in this study via the ciliary somatostatin receptor 3 (SSTR3). Primary cilia are membrane organelles that act as signaling hubs in islets by virtue of their subcellular location and enrichment in signaling proteins such as G-protein coupled receptors (GPCRs). We show that SSTR3, a ciliary GPCR, mediates somatostatin suppression of insulin secretion in mouse islets. Quantitative analysis of calcium flux using a mouse model of genetically encoded beta cell-specific GCaMP6f calcium reporter shows that somatostatin signaling alters beta cell calcium flux after physiologic glucose stimulation, an effect that depends on endogenous SSTR3 expression and the presence of intact primary cilia on beta cells. Comparative
    MeSH term(s) Cilia ; Glucose ; Receptors, Somatostatin ; Somatostatin ; Animals ; Mice
    Chemical Substances Glucose (IY9XDZ35W2) ; Receptors, Somatostatin ; Somatostatin (51110-01-1) ; somatostatin receptor 3
    Language English
    Publishing date 2023-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2589489-4
    ISSN 1938-2022 ; 1938-2022
    ISSN (online) 1938-2022
    ISSN 1938-2022
    DOI 10.1080/19382014.2023.2252855
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Islet cilia and glucose homeostasis

    Isabella Melena / Jing W. Hughes

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: Diabetes is a growing pandemic affecting over ten percent of the U.S. population. Individuals with all types of diabetes exhibit glucose dysregulation due to altered function and coordination of pancreatic islets. Within the critical intercellular space ... ...

    Abstract Diabetes is a growing pandemic affecting over ten percent of the U.S. population. Individuals with all types of diabetes exhibit glucose dysregulation due to altered function and coordination of pancreatic islets. Within the critical intercellular space in pancreatic islets, the primary cilium emerges as an important physical structure mediating cell-cell crosstalk and signal transduction. Many events leading to hormone secretion, including GPCR and second-messenger signaling, are spatiotemporally regulated at the level of the cilium. In this review, we summarize current knowledge of cilia action in islet hormone regulation and glucose homeostasis, focusing on newly implicated ciliary pathways that regulate insulin exocytosis and intercellular communication. We present evidence of key signaling proteins on islet cilia and discuss ways in which cilia might functionally connect islet endocrine cells with the non-endocrine compartments. These discussions aim to stimulate conversations regarding the extent of cilia-controlled glucose homeostasis in health and in metabolic diseases.
    Keywords primary cilia ; beta cells ; pancreatic islets ; paracrine signaling ; glucose regulation ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Scanning electron microscopy of human islet cilia.

    Polino, Alexander J / Sviben, Sanja / Melena, Isabella / Piston, David W / Hughes, Jing W

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 22, Page(s) e2302624120

    Abstract: Human islet primary cilia are vital glucose-regulating organelles whose structure remains uncharacterized. Scanning electron microscopy (SEM) is a useful technique for studying the surface morphology of membrane projections like cilia, but conventional ... ...

    Abstract Human islet primary cilia are vital glucose-regulating organelles whose structure remains uncharacterized. Scanning electron microscopy (SEM) is a useful technique for studying the surface morphology of membrane projections like cilia, but conventional sample preparation does not reveal the submembrane axonemal structure, which holds key implications for ciliary function. To overcome this challenge, we combined SEM with membrane-extraction techniques to examine primary cilia in native human islets. Our data show well-preserved cilia subdomains which demonstrate both expected and unexpected ultrastructural motifs. Morphometric features were quantified when possible, including axonemal length and diameter, microtubule conformations, and chirality. We further describe a ciliary ring, a structure that may be a specialization in human islets. Key findings are correlated with fluorescence microscopy and interpreted in the context of cilia function as a cellular sensor and communications locus in pancreatic islets.
    MeSH term(s) Humans ; Microscopy, Electron, Scanning ; Cilia/physiology ; Microscopy, Fluorescence ; Islets of Langerhans ; Microtubules
    Language English
    Publishing date 2023-05-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2302624120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  8. Article: Scanning electron microscopy of human islet cilia.

    Polino, Alexander J / Sviben, Sanja / Melena, Isabella / Piston, David W / Hughes, Jing

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Human islet primary cilia are vital glucose-regulating organelles whose structure remains uncharacterized. Scanning electron microscopy (SEM) is a useful technique for studying the surface morphology of membrane projections like primary cilia, but ... ...

    Abstract Human islet primary cilia are vital glucose-regulating organelles whose structure remains uncharacterized. Scanning electron microscopy (SEM) is a useful technique for studying the surface morphology of membrane projections like primary cilia, but conventional sample preparation does not reveal the sub-membrane axonemal structure which holds key implications for cilia function. To overcome this challenge, we combined SEM with membrane-extraction techniques to examine cilia in native human islets. Our data show well-preserved cilia subdomains which demonstrate both expected and unexpected ultrastructural motifs. Morphometric features were quantified when possible, including axonemal length and diameter, microtubule conformations and chirality. We further describe a novel ciliary ring, a structure that may be a specialization in human islets. Key findings are correlated with fluorescence microscopy and interpreted in the context of cilia function as a cellular sensor and communications locus in pancreatic islets.
    Language English
    Publishing date 2023-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.15.528685
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Fluorescence imaging of beta cell primary cilia.

    Li, Zipeng A / Cho, Jung Hoon / Woodhams, Louis G / Hughes, Jing W

    Frontiers in endocrinology

    2022  Volume 13, Page(s) 1004136

    Abstract: Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely ...

    Abstract Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods that we have adopted and optimized for the observation of primary cilia in mouse and human islets. These include conventional confocal microscopy using fixed islets and pancreas sections, live-cell imaging with cilia-targeted biosensors and probes, cilia motion recordings, and quantitative analysis of primary cilia waveform in the
    MeSH term(s) Animals ; Cilia/metabolism ; Humans ; Insulin Secretion ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/diagnostic imaging ; Mice ; Optical Imaging
    Language English
    Publishing date 2022-09-23
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.1004136
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Modeling the genomic complexity of human cancer using Cas12a mice.

    Hebert, Jess D / Xu, Haiqing / Tang, Yuning J / Ruiz, Paloma A / Detrick, Colin / Wang, Jing / Hughes, Nicholas W / Donosa, Oscar / Andrejka, Laura / Karmakar, Saswati / Aboiralor, Irenosen / Cong, Le / Sage, Julien / Petrov, Dmitri A / Winslow, Monte M

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Somatic genome editing in mouse models has increased our understanding of ... ...

    Abstract Somatic genome editing in mouse models has increased our understanding of the
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.07.583774
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