in-vivo-imaging-liver-spheroids-engrafted-anterior-chamber-mouse

In Vivo Imaging of Liver Spheroids Engrafted in the Anterior Chamber of the Mouse Eye

Biomedical studies of the liver in mammals are hindered by the lack of methods for in vivo noninvasive longitudinal imaging at cellular resolution. Until ...

An oscillatory increase in pancreatic beta cell cytoplasmic free Ca2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel beta3 subunit in the molecular regulation of these [Ca2+]i oscillations has now been clarified by using beta3 subunit-deficient beta cells. beta3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in beta cells lacking the beta3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the beta3 subunit negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the beta3 subunit in the beta cell may constitute the basis for a novel diabetes therapy.

Removal of Ca2+ channel beta3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis.

Eine oszillierende Zunahme der Betazellen zytoplasmatischen freie Ca2 + Konzentration, [Ca2 +] i, ist ein wichtiges Feature in induziert durch Glukose-Insulin-Freisetzung. Die Rolle von der Spannung-Gating Ca2 + Kanal beta3 Untereinheit in der molekularen Verordnung von diesen [Ca2 +] ich Schwingungen hat jetzt mit beta3 Untereinheit-defizienten Betazellen gekl&auml;rt. beta3-Knockout-M&auml;use zeigten eine effizientere Glukose-Hom&ouml;ostase im Vergleich zu Wildtyp M&auml;usen durch erh&ouml;hte Glukose stimuliert Insulin-Sekretion. Dies resultierte aus einer erh&ouml;hten Glukose-induzierte [Ca2 +] i Schwingungsfrequenz in Beta-Zellen fehlt die beta3-Untereinheit, ein Effekt durch verst&auml;rkte Bildung von Inosit 1,4,5-Trisphosphate (InsP3) entfielen und erh&ouml;hte Ca2 +-Mobilisierung von den intrazellul&auml;ren speichern. Daher moduliert die beta3-Untereinheit negativ InsP3-induced Ca2 + Release, die nicht durch irgendwelche Auswirkungen auf die Spannung-Gating L-Typ Ca2 +-Kanal Parallel ist. Da die Erh&ouml;hung der Insulin-Freisetzung nur bei hohen Glukose-Konzentrationen manifestiert wurde, kann die Blockierung der beta3-Untereinheit in der Beta-Zelle die Basis f&uuml;r eine neuartige Diabetestherapie darstellen.

Entfernung von Ca2 + Kanal beta3 Untereinheit erh&ouml;ht Ca2 + Schwingungsfrequenz und Exozytose von Insulin.

The monomeric G-protein, Rhes, is a candidate imidazoline-regulated molecule involved in mediating the insulin secretory response to efaroxan [S.L. Chan, L.K. Monks, H. Gao, P. Deaville, N.G. Morgan, Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell, Br. J. Pharmacol. 136 (1) (2002) 31-36]. This suggestion was based on observations regarding changes in Rhes mRNA expression in rat islets and pancreatic beta-cells after prolonged culture with efaroxan, leading to desensitization of the insulin response to the compound. To verify this report, we have evaluated the effects of the imidazoline compounds efaroxan and BL11282 on Rhes mRNA expression in isolated rat pancreatic islets maintained in conditions identical to those used by Chan et al. The results demonstrate that desensitization of the insulin response to efaroxan, or to another imidazoline, BL11282, does not change Rhes mRNA expression levels. Transfection of MIN6 cells with plasmids containing Rhes or Rhes-antisense also does not alter efaroxan- or BL11282-induced insulin secretion. Together, these data do not support the hypothesis that Rhes is an imidazoline-regulated protein.

Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic beta-cells.

Das Monomere G-Protein, Rhes, ist ein Kandidat Imidazoline regulierte Molek&uuml;l beteiligt bei der Vermittlung der sekretorischen Insulin-Reaktion auf Efaroxan [S.L. Chan, l.k.-M&ouml;nche, H. Gao, s. Deaville, n.g. Morgan, Identifizierung des Monomer G-Proteins, Rhes, als ein Efaroxan regulierte Protein in der-Betazellen, Br. J. Pharmacol. 136 (1) (2002) 31-36]. Dieser Vorschlag basiert auf Beobachtungen bez&uuml;glich &Auml;nderungen in Rhes mRNA Ausdruck in Ratte Inselchen und pankreatischen Betazellen nach l&auml;ngerer Kultur mit Efaroxan, f&uuml;hrt zu Desensibilisierung der Insulin-Reaktion auf das Gel&auml;nde. Um diesen Bericht zu &uuml;berpr&uuml;fen, haben wir die Auswirkungen der Imidazoline Verbindungen Efaroxan und BL11282 &uuml;ber Rhes mRNA Ausdruck in isolierten Ratte Pankreas Inselchen in Bedingungen identisch mit denen von Chan Et al. verwaltet bewertet. Die Ergebnisse zeigen, dass Desensibilisierung der Insulin-Antwort auf Efaroxan oder auf einem anderen Imidazoline, BL11282, Rhes mRNA Ausdruck Niveaus nicht &auml;ndert. MIN6 Zellen mit Plasmide mit Rhes oder Rhes-Antisense ebenfalls ver&auml;ndert nicht die Efaroxan oder BL11282-induzierter Insulin-Sekretion. Gemeinsam unterst&uuml;tzen diese Daten nicht die Hypothese, dass Rhes ein Imidazoline regulierte Protein ist.

Monomer G-Protein, Rhes, ist kein Imidazoline regulierte Protein in pankreatischen Betazellen.

Advanced imaging techniques have become a valuable tool in the study of complex biological processes at the cellular level in biomedical research. Here, we introduce a new technical platform for noninvasive in vivo fluorescence imaging of pancreatic islets using the anterior chamber of the eye as a natural body window. Islets transplanted into the mouse eye engrafted on the iris, became vascularized, retained cellular composition, responded to stimulation and reverted diabetes. Laser-scanning microscopy allowed repetitive in vivo imaging of islet vascularization, beta cell function and death at cellular resolution. Our results thus establish the basis for noninvasive in vivo investigations of complex cellular processes, like beta cell stimulus-response coupling, which can be performed longitudinally under both physiological and pathological conditions.

Noninvasive in vivo imaging of pancreatic islet cell biology.

Erweiterte bildgebende Verfahren sind ein wertvolles Instrument in der Studie der komplexen biologischen Prozesse auf zellul&auml;rer Ebene in der biomedizinischen Forschung geworden. Hier stellen wir eine neue technische Plattform f&uuml;r nicht-invasive in-vivo Fluoreszenz-Imaging pankreatischen kleinen Inseln, die mit die Vorderkammer des Auges als einem nat&uuml;rlichen K&ouml;rper-Fenster. Inselchen transplantierte in das Maus-Auge Abbau auf der Iris, wurde vascularized, zellul&auml;re Zusammensetzung beibehalten, reagierte auf die Stimulation und Diabetes zur&uuml;ckgesetzt. Laser-Rastermikroskopie erlaubt sich wiederholende in-vivo Bildgebung von Inselchen Vaskularisierung, Beta-Zellfunktion und Tod bei zellul&auml;ren Aufl&ouml;sung. Unsere Ergebnisse schaffen damit die Grundlage f&uuml;r die nicht-invasive in-vivo Untersuchungen komplexer zellul&auml;rer Prozesse, wie Beta-Zelle Stimulus-Antwort Kupplung, die in L&auml;ngsrichtung unter sowohl physiologischen und pathologischen Bedingungen durchgef&uuml;hrt werden kann.

Nicht-invasive in-vivo Bildgebung des Pankreas Inselchen Zellbiologie.

Pancreatic alpha cells contribute to glucose homeostasis by the regulated secretion of glucagon, which increases glycogenolysis and hepatic gluconeogenesis in response to hypoglycemia. Alterations of glucagon secretion are observed in diabetic patients and exacerbate the disease. The restricted availability of purified primary alpha cells has limited our understanding of their function in health and disease. This study was designed to establish convenient protocols for the purification of viable alpha cells from rat and human pancreatic islets by FACS, using intrinsic cellular properties. Islets were isolated from the pancreata of Wistar rats or deceased human organ donors. Dispersed islet cells were separated by FACS based on light scatter and autofluorescence. Purity of sorted cells was evaluated by immunocytochemistry using hormone specific antibodies. Relative hormone expression was further determined by quantitative RT-PCR. Viability was determined by Annexin V and propidium iodide staining and function was assessed by monitoring cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) using Fura-2/AM. We developed species-specific FACS gating strategies that resulted in populations consisting mainly of alpha cells (96.6 Â± 1.4%, n = 3 for rat; 95.4 Â± 1.7%, n = 4 for human, mean Â± SEM). These cell fractions showed ~5-fold and ~4-fold enrichment (rat and human, respectively) of glucagon mRNA expression compared to total ungated islet cells. Most of the sorted cells were viable and functional, as they responded with an increase in [Ca(2+)](i) upon stimulation with L-arginine (10 mM). The majority of the sorted human alpha cells responded also to stimulation with kainate (100 Î¼M), whereas this response was infrequent in rat alpha cells. Using the same sample preparation, but a different gating strategy, we were also able to sort rat and human populations enriched in beta cells. In conclusion, we have simplified and optimized a method for the purification of rat alpha cells, as well as established a novel approach to separate human alpha cells using neither antibodies nor dyes possibly interfering with cellular functions.

One-step purification of functional human and rat pancreatic alpha cells.

Pankreas Alphazellen beitragen zu Glukose Hom&ouml;ostase, indem die regulierte Sekretion von Glucagon, die Glykogenolyse und hepatische Glukoneogenese als Reaktion auf Hypoglyk&auml;mie erh&ouml;ht. &Auml;nderungen der Glucagon-Sekretion bei diabetischen Patienten eingehalten werden und die Krankheit verschlimmern. Die eingeschr&auml;nkte Verf&uuml;gbarkeit von gereinigtem prim&auml;re Alphazellen hat unser Verst&auml;ndnis ihrer Funktion in Gesundheit und Krankheit beschr&auml;nkt. Diese Studie wurde von FACS, mit zellul&auml;re Eigenschaften herstellen bequem Protokolle f&uuml;r die Reinigung der tragf&auml;hige Alphazellen von Ratte und menschlichen Pankreas Inselchen entworfen. Inselchen wurden isoliert von der Pancreata der Wistar-Ratten oder verstorbenen menschliche Organspender. Verteilte Inselzellen waren durch FACS basierend auf Lichtstreuung und Autofluoreszenz getrennt. Reinheit der sortierten Zellen wurde von Immunzytochemie mit Hormon spezifische Antik&ouml;rper evaluiert. Relative Hormon Ausdruck wurde weiter von quantitativen RT-PCR bestimmt. Lebensf&auml;higkeit von Annexin V bestimmt wurde und Propidium Jodid F&auml;rbe- und Funktion wurde ermittelt, indem die &Uuml;berwachung zytoplasmatischen kostenlose Ca(2+) Konzentration ([Ca(2+)](i)) mit Fura-2/AM. Wir entwickelten artspezifische FACS Anspritzung Strategien, die in Populationen mit vorwiegend Alphazellen gef&uuml;hrt (96.6 &plusmn; 1,4 %, n = 3 f&uuml;r Ratte; 95.4 &plusmn; 1,7 %, n = 4 f&uuml;r Mensch, Mittelwert &plusmn; SEM). Diese Handy-Fraktionen zeigte ~ 5-fold und ~ 4fach gefaltete Anreicherung (Ratte und Mensch, beziehungsweise) von Glukagon mRNA Ausdruck im Vergleich zur gesamten ungated Inselzellen. Die meisten sortierten Zellen waren lebensf&auml;hig und funktional, wie sie reagiert mit einer Zunahme [Ca(2+)](i) nach Stimulation mit L-Arginin (10 mM). Die meisten der sortierten menschlichen Alphazellen reagierte auch auf Stimulation mit Kainate (100 &mu;M), w&auml;hrend diese Antwort in Ratte Alphazellen Schwurgerichtsverfahren. Mit der gleichen Probenvorbereitung, aber eine andere gating Strategie, konnten wir auch Art Ratte und menschlichen Populationen in Beta-Zellen angereichert. Abschlie&szlig;end haben wir vereinfacht und optimiert eine Methode f&uuml;r die Reinigung der Ratte Alphazellen sowie einen neuartigen Ansatz um menschliche Alphazellen mit Antik&ouml;rpern weder Farbstoffe, die m&ouml;glicherweise st&ouml;ren Zellfunktionen zu trennen eingef&uuml;hrt.

Einstufige Reinigung der funktionale Mensch und Ratte Pankreas Alphazellen.

Type 2 diabetes mellitus is affecting more than 382 million people worldwide. Although much progress has been made, a comprehensive understanding of the underlying disease mechanism is still lacking. Here we report a role for the β-cell primary cilium in type 2 diabetes susceptibility. We find impaired glucose handling in young Bbs4(-/-) mice before the onset of obesity. Basal body/ciliary perturbation in murine pancreatic islets leads to impaired first phase insulin release ex and in vivo. Insulin receptor is recruited to the cilium of stimulated β-cells and ciliary/basal body integrity is required for activation of downstream targets of insulin signalling. We also observe a reduction in the number of ciliated β-cells along with misregulated ciliary/basal body gene expression in pancreatic islets in a diabetic rat model. We suggest that ciliary function is implicated in insulin secretion and insulin signalling in the β-cell and that ciliary dysfunction could contribute to type 2 diabetes susceptibility.

Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents.

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+)]i response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of β-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus. 

Apolipoprotein CIII links islet insulin resistance to β-cell failure in diabetes.

Nature's fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5's active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases.

Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins.

The two insulin receptor (IR) isoforms IR-A and IR-B are responsible for the pleiotropic actions of insulin and insulin-like growth factors. Consequently, changes in IR isoform expression and in the bioavailability of their ligands will impact on IR-mediated functions. Although alteration of IR isoform expression has been linked to insulin resistance, knowledge of IR isoform expression and mechanisms underlying tissue/cell-type-specific changes in metabolic disease are lacking. Using mouse models of obesity/diabetes and measuring the mRNA of the IR isoforms and mRNA/protein levels of total IR, we provide a data set of IR isoform expression pattern that documents changes in a tissue-dependent manner. Combining tissue fractionation and a new in situ mRNA hybridization technology to visualize the IR isoforms at cellular resolution, we explored the mechanism underlying the change in IR isoform expression in perigonadal adipose tissue, which is mainly caused by tissue remodelling, rather than by a shift in IR alternative splicing in a particular cell type, e.g. adipocytes.

Tissue-specific expression of insulin receptor isoforms in obesity/type 2 diabetes mouse models.

ATP-sensitive K (K) channels couple cellular metabolism to electrical activity in many cell types. Wild-type K channels are comprised of four pore forming (Kir6.x) and four regulatory (sulfonylurea receptor, SURx) subunits that each contain RKR endoplasmic reticulum retention sequences that serve to properly translocate the channel to the plasma membrane. Truncated Kir6.x variants lacking RKR sequences facilitate plasma membrane expression of functional Kir6.x in the absence of SURx; however, the effects of channel truncation on plasma membrane orientation have not been explored. To investigate the role of truncation on plasma membrane orientation of ATP sensitive K channels, three truncated variants of Kir6.2 were used (Kir6.2ΔC26, 6xHis-Kir6.2ΔC26, and 6xHis-EGFP-Kir6.2ΔC26). Oocyte expression of Kir6.2ΔC26 shows the presence of a population of inverted inserted channels in the plasma membrane, which is not present when co-expressed with SUR1. Immunocytochemical staining of intact and permeabilized HEK293 cells revealed that the N-terminus of 6xHis-Kir6.2ΔC26 was accessible on both sides of the plasma membrane at roughly equivalent ratios, whereas the N-terminus of 6xHis-EGFP-Kir6.2Δ26 was only accessible on the intracellular face. In HEK293 cells, whole-cell electrophysiological recordings showed a ca. 50% reduction in K current upon addition of ATP to the extracellular solution for 6xHis-Kir6.2ΔC26, though sensitivity to extracellular ATP was not observed in 6xHis-EGFP-Kir6.2ΔC26. Importantly, the population of channels that is inverted exhibited similar function to properly inserted channels within the plasma membrane. Taken together, these data suggest that in the absence of SURx, inverted channels can be formed from truncated Kir6.x subunits that are functionally active which may provide a new model for testing pharmacological modulators of Kir6.x, but also indicates the need for added caution when using truncated Kir6.2 mutants.

Expression of truncated Kir6.2 promotes insertion of functionally inverted ATP-sensitive K channels.

The ATP-sensitive K (K(ATP)) channel is found in a variety of tissues extending from the heart and vascular smooth muscles to the endocrine pancreas and brain. Common to all K(ATP) channels is the pore-forming subunit Kir6.x, a member of the family of small inwardly rectifying K channels, and the regulatory subunit sulfonylurea receptor (SURx). In insulin secreting β-cells in the endocrine part of the pancreas, where the channel is best studied, the K(ATP) channel consists of Kir6.2 and SUR1. Under physiological conditions, the K(ATP) channel current flow is outward at membrane potentials more positive than the K equilibrium potential around -80 mV. However, K(ATP) channel kinetics have been extensively investigated for inward currents and the single-channel kinetic model is based on this type of recording, whereas only a limited amount of work has focused on outward current kinetics.

Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties.

Primary cilia have recently emerged as cellular signaling organelles. Their homeostasis and function require a high amount of energy. However, how energy depletion and mitochondria impairment affect cilia have barely been addressed. We first studied the spatial relationship between a mitochondria subset in proximity to the cilium in vitro, finding similar mitochondrial activity measured as mitochondrial membrane potential compared with the cellular network. Next, using common primary cilia cell models and inhibitors of mitochondrial energy production, we found alterations in cilia number and/or length due to energy depletion and mitochondrial reactive oxygen species (ROS) overproduction. Finally, by using a mouse model of type 2 diabetes mellitus, we provided in vivo evidence that cilia morphology is impaired in diabetic nephropathy, which is characterized by ROS overproduction and impaired mitochondrial metabolism. In conclusion, we showed that energy imbalance and mitochondrial ROS affect cilia morphology and number, indicating that conditions characterized by mitochondria and radicals imbalances might lead to ciliary impairment.

Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology.

Pancreatic islets are micro-organs composed of a mixture of endocrine and non-endocrine cells, where the former secrete hormones and peptides necessary for metabolic homeostasis. Through vasculature and innervation the cells within the islets are in communication with the rest of the body, while they interact with each other through juxtacrine, paracrine and autocrine signals, resulting in fine-tuned sensing and response to stimuli. In this context, cellular protrusion in islet cells, such as primary cilia and filopodia, have gained attention as potential signaling hubs. During the last decade, several pieces of evidence have shown how the primary cilium is required for islet vascularization, function and homeostasis. These findings have been possible thanks to the development of ciliary/basal body specific knockout models and technological advances in microscopy, which allow longitudinal monitoring of engrafted islets transplanted in the anterior chamber of the eye in living animals. Using this technique in combination with optogenetics, new potential paracrine interactions have been suggested. For example, reshaping and active movement of filopodia-like protrusions of δ-cells were visualized in vivo, suggesting a continuous cell remodeling to increase intercellular contacts. In this review, we discuss these recent discoveries regarding primary cilia and filopodia and their role in islet homeostasis and intercellular islet communication.

Novel aspects of intra-islet communication: Primary cilia and filopodia.

Multiple inositol polyphosphate phosphatase (MINPP1) is an enigmatic enzyme that is responsible for the metabolism of inositol hexakisphosphate (Ins) and inositol 1,3,4,5,6 pentakisphosphate (Ins(1,3,4,5,6) in mammalian cells, despite being restricted to the confines of the ER. The reason for this compartmentalization is unclear. In our previous studies in the insulin-secreting HIT cell line, we expressed MINPP1 in the cytosol to artificially reduce the concentration of these higher inositol phosphates. Undocumented at the time, we noted cytosolic MINPP1 expression reduced cell growth. We were struck by the similarities in substrate preference between a number of different enzymes that are able to metabolize both inositol phosphates and lipids, notably IPMK and PTEN. MINPP1 was first characterized as a phosphatase that could remove the 3-phosphate from inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)) This molecule shares strong structural homology with the major product of the growth-promoting Phosphatidyl 3-kinase (PI3K), phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)) and PTEN can degrade both this lipid and Ins(1,3,4,5). Because of this similar substrate preference, we postulated that the cytosolic version of MINPP1 (cyt-MINPP1) may not only attack inositol polyphosphates but also PtdIns(3,4,5), a key signal in mitogenesis. Our experiments show that expression of cyt-MINPP1 in HIT cells lowers the concentration of PtdIns(3,4,5). We conclude this reflects a direct effect of MINPP1 upon the lipid because cyt-MINPP1 actively dephosphorylates synthetic, di(C4:0)PtdIns(3,4,5) in vitro. These data illustrate the importance of MINPP1's confinement to the ER whereby important aspects of inositol phosphate metabolism and inositol lipid signaling can be separately regulated and give one important clarification for MINPP1's ER seclusion.

Article	Year
Removal of Ca2+ channel beta3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis. Cell\| PubMed ID: 15479643	2004
Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic beta-cells. Biochemical and biophysical research communications\| PubMed ID: 16277977	2005
Noninvasive in vivo imaging of pancreatic islet cell biology. Nature medicine\| PubMed ID: 18327249	2008
One-step purification of functional human and rat pancreatic alpha cells. Integrative biology : quantitative biosciences from nano to macro\| PubMed ID: 22267247	2012
Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents. Nature communications\| PubMed ID: 25374274	2014
Apolipoprotein CIII links islet insulin resistance to β-cell failure in diabetes. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 25941406	2015
Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. PLoS genetics\| PubMed ID: 26352669	2015
Tissue-specific expression of insulin receptor isoforms in obesity/type 2 diabetes mouse models. Journal of cellular and molecular medicine\| PubMed ID: 33742502	2021
Expression of truncated Kir6.2 promotes insertion of functionally inverted ATP-sensitive K channels. Scientific reports\| PubMed ID: 34728728	2021
Inward and outward currents of native and cloned K(ATP) channels (Kir6.2/SUR1) share single-channel kinetic properties. Biochemistry and biophysics reports\| PubMed ID: 35434386	2022
Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology. Life science alliance\| PubMed ID: 36104081	2022
Novel aspects of intra-islet communication: Primary cilia and filopodia. Advances in biological regulation\| PubMed ID: 36266190	2023
Multiple Inositol Polyphosphate Phosphatase Compartmentalization Separates Inositol Phosphate Metabolism from Inositol Lipid Signaling. Biomolecules\| PubMed ID: 37371464	2023

Barbara Leibiger

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