scholarly journals Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slices

Author(s):  
Andraz Stozer ◽  
Maša Skelin Klemen ◽  
Marko Gosak ◽  
Lidija Križančić Bombek ◽  
Viljem Pohorec ◽  
...  

Many details of glucose-stimulated intracellular calcium changes in beta cells during activation, activity, and deactivation, as well as their concentration-dependence, remain to be analyzed. Classical physiological experiments indicated that in islets, functional differences between individual cells are largely attenuated, but recent findings suggest considerable intercellular heterogeneity, with some cells possibly coordinating the collective responses. To address the above with an emphasis on heterogeneity and describing the relations between classical physiological and functional network properties, we performed functional multicellular calcium imaging in mouse pancreas tissue slices over a wide range of glucose concentrations. During activation, delays to activation of cells and any-cell-to-first-responder delays shortened, and the sizes of simultaneously responding clusters increased with increasing glucose. Exactly the opposite characterized deactivation. The frequency of fast calcium oscillations during activity increased with increasing glucose up to 12 mM glucose, beyond which oscillation duration became longer, resulting in a homogenous increase in active time. In terms of functional connectivity, islets progressed from a very segregated network to a single large functional unit with increasing glucose. A comparison between classical physiological and network parameters revealed that the first-responders during activation had longer active times during plateau and the most active cells during the plateau tended to deactivate later. Cells with the most functional connections tended to activate sooner, have longer active times, and deactivate later. Our findings provide a common ground for recent differing views on beta cell heterogeneity and an important baseline for future studies of stimulus-secretion and intercellular coupling.

2020 ◽  
Author(s):  
Jurij Dolenšek ◽  
Maša Skelin Klemen ◽  
Marko Gosak ◽  
Lidija Križančić-Bombek ◽  
Viljem Pohorec ◽  
...  

AbstractGlucose progressively stimulates insulin release over a wide range of concentrations. However, the nutrient coding underlying activation, activity, and deactivation of beta cells affecting insulin release remains only partially described. Experimental data indicate that nutrient sensing in coupled beta cells in islets is predominantly a collective trait, overriding to a large extent functional differences between cells. However, some degree of heterogeneity between coupled beta cells may play important roles. To further elucidate glucose-dependent modalities in coupled beta cells, the degree of functional heterogeneity, and uncover the emergent collective operations, we combined acute mouse pancreas tissue slices with functional multicellular calcium imaging. We recorded beta cell calcium responses from threshold (7 mM) to supraphysiological (16 mM) glucose concentrations with high spatial and temporal resolution. This enabled the analysis of both classical physiological parameters and complex network parameters, as well as their comparison at the level of individual cells. The activation profile displayed two major glucose concentration-dependent features, shortening of delays to initial activation, and shortening of delays until half activation with increasing glucose concentration. Inversely, during deactivation both delays to initial deactivation and until half deactivation were progressively longer with increasing glucose concentration. The plateau activity with fast calcium oscillations expressed two types of glucose-dependence. Physiological concentrations mostly affected the frequency of oscillations, whereas supraphysiological concentrations progressively prolonged the duration of oscillations. Most of the measured functional network parameters also showed clear glucose-dependence. In conclusion, we propose novel understanding for glucose-dependent coding properties in beta cell networks, and its deciphering may have repercussions for our understanding of the normal physiology of glucose homeostasis as well as of disturbances of metabolic homeostasis, such as diabetes mellitus.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e82374 ◽  
Author(s):  
Jurij Dolenšek ◽  
Andraž Stožer ◽  
Maša Skelin Klemen ◽  
Evan W. Miller ◽  
Marjan Slak Rupnik

2022 ◽  
Author(s):  
Viljem Pohorec ◽  
Lidija Krizancic Bombek ◽  
Masa Skelin Klemen ◽  
Jurij Dolensek ◽  
Andraz Stozer

Although mice are a very instrumental model in islet beta cell research, possible phenotypic differences between strains and substrains are largely neglected in the scientific community. In this study, we show important phenotypic differences in beta cell responses to glucose between NMRI, C57BL/6J, and C57BL/6N mice, i.e., the three most commonly used strains. High-resolution multicellular confocal imaging of beta cells in acute pancreas tissue slices was used to measure and quantitatively compare the calcium dynamics in response to a wide range of glucose concentrations. Strain- and substrain-specific features were found in all three phases of beta cell responses to glucose: a shift in the dose-response curve characterizing the delay to activation and deactivation in response to stimulus onset and termination, respectively, and distinct concentration-encoding principles during the plateau phase in terms of frequency, duration, and active time changes with increasing glucose concentrations. Our results underline the significance of carefully choosing and reporting the strain to enable comparison and increase reproducibility, emphasize the importance of analyzing a number of different beta cell physiological parameters characterizing the response to glucose, and provide a valuable standard for future studies on beta cell calcium dynamics in health and disease.


2011 ◽  
Vol 589 (2) ◽  
pp. 395-408 ◽  
Author(s):  
Ya-Chi Huang ◽  
Marjan Rupnik ◽  
Herbert Y. Gaisano

Author(s):  
Barbara Wrzesińska ◽  
Agnieszka Zmienko ◽  
Lam Dai Vu ◽  
Ive De Smet ◽  
Aleksandra Obrępalska-Stęplowska

Abstract Key message PSV infection changed the abundance of host plant’s transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and cytosol, affecting photosynthesis, translation, transcription, and splicing. Abstract Virus infection is a process resulting in numerous molecular, cellular, and physiological changes, a wide range of which can be analyzed due to development of many high-throughput techniques. Plant RNA viruses are known to replicate in the cytoplasm; however, the roles of chloroplasts and other cellular structures in the viral replication cycle and in plant antiviral defense have been recently emphasized. Therefore, the aim of this study was to analyze the small RNAs, transcripts, proteins, and phosphoproteins affected during peanut stunt virus strain P (PSV-P)–Nicotiana benthamiana interactions with or without satellite RNA (satRNA) in the context of their cellular localization or functional connections with particular cellular compartments to elucidate the compartments most affected during pathogenesis at the early stages of infection. Moreover, the processes associated with particular cell compartments were determined. The ‘omic’ results were subjected to comparative data analyses. Transcriptomic and small RNA (sRNA)–seq data were obtained to provide new insights into PSV-P–satRNA–plant interactions, whereas previously obtained proteomic and phosphoproteomic data were used to broaden the analysis to terms associated with cellular compartments affected by virus infection. Based on the collected results, infection with PSV-P contributed to changes in the abundance of transcripts and proteins associated with various cellular compartments, including ribosomes, chloroplasts, mitochondria, the nucleus and the cytosol, and the most affected processes were photosynthesis, translation, transcription, and mRNA splicing. Furthermore, sRNA-seq and phosphoproteomic analyses indicated that kinase regulation resulted in decreases in phosphorylation levels. The kinases were associated with the membrane, cytoplasm, and nucleus components.


2017 ◽  
Vol 57 (2) ◽  
pp. 151
Author(s):  
Paul Fehrmann

It is clear that the world of Islam is profoundly important, and also that there are wide and conflicting views on Islam today. Similarly, it seems clear that we should pursue efforts to promote the understanding of Islam. In response, a goal of the four volume Islam: A Worldwide Encyclopedia (IAWE) is to give “basic information on Islam” and to “shed light” on “controversial issues” (xxvii). In his opening comments, the editor, a Professor of International Law and Politics at Eskişehir Osmangazi University and Senior Researcher at the Wise Men Center for Strategic Research in Turkey, notes that there have been “a wide range of different interpretations and variations of Islam throughout history” (xxvii). He suggests that Muslims need to revive the “strong tradition of academic debate” that was integral to Islamic studies “in early decades of Islam,” and affirms support for the “diverse and plural nature of contemporary Islamic scholarship” (xxviii). At the same time, he is concerned that “disputed issues” may lead to “biases and stereotypes in the minds of Western people,” and hopes that this new resource can both “contribute to the pursuit of a common ground” between those of different faiths, and help a Western audience become more familiar with what Islam has to offer (xxviii).


2021 ◽  
pp. 159101992110402
Author(s):  
Muhammad U. Manzoor ◽  
Ibrahim A. Almulhim ◽  
Abdullah A. Alrashed ◽  
Abdulrahman Y. Alturki ◽  
Fatimah A. Alghabban ◽  
...  

Background Recently, radial artery access has gained popularity for interventional neurovascular procedures due to patient comfort and fewer complications. However, there are instances where the radial artery approach is not feasible. In such cases, trans-ulnar artery access (TUA) can offer an alternate route. There is limited data regarding neuro-interventional procedures performed via this approach. This study aims to evaluate the feasibility and safety of trans-ulnar approach for a wide range of interventional neurovascular procedures. Materials and methods The data for all patients who underwent ulnar artery access for diagnostic or interventional neuroradiology procedures was retrospectively collected between September 2020 and March 2021. Patient demographics, procedural details, procedure success, and complications were recorded. Results During the study period, 23 patients underwent 24 trans-ulnar approach procedures. The mean age of patients was 50.1 ± 14.2 years. Fourteen diagnostic cerebral angiograms and ten interventional procedures were performed. All procedures were successfully completed via trans-ulnar approach without a switch to alternate access. No major access site complication was observed. Conclusion Ulnar artery access is a safe and feasible option for neurovascular procedures. It can be effectively utilized for diagnostic cerebral angiography and a wide range of interventional procedures.


Author(s):  
Robert Stern ◽  
Nicholas Walker

As an intellectual tradition, the history of Hegelianism is the history of the reception and influence of the thought of G.W.F. Hegel. This tradition is notoriously complex and many-sided, because while some Hegelians have seen themselves as merely defending and developing his ideas along what they took to be orthodox lines, others have sought to ‘reform’ his system, or to appropriate individual aspects and overturn others, or to offer consciously revisionary readings of his work. This makes it very hard to identify any body of doctrine common to members of this tradition, and a wide range of divergent philosophical views can be found among those who (despite this) can none the less claim to be Hegelians. There are both ‘internal’ and ‘external’ reasons for this: on one hand, Hegel’s position itself brings together many different tendencies (idealism and objectivism, historicism and absolutism, rationalism and empiricism, Christianity and humanism, classicism and modernism, a liberal view of civil society with an organicist view of the state); any balance between them is hermeneutically very unstable, enabling existing readings to be challenged and old orthodoxies to be overturned. On the other hand, the critical response to Hegel’s thought and the many attempts to undermine it have meant that Hegelians have continually needed to reconstruct his ideas and even to turn Hegel against himself, while each new intellectual development, such as Marxism, pragmatism, phenomenology or existential philosophy, has brought about some reassessment of his position. This feature of the Hegelian tradition has been heightened by the fact that Hegel’s work has had an impact at different times over a long period and in a wide range of countries, so that divergent intellectual, social and historical pressures have influenced its distinct appropriations. At the hermeneutic level, these appropriations have contributed greatly to keeping the philosophical understanding of Hegel alive and open-ended, so that our present-day conception of his thought cannot properly be separated from them. Moreover, because questions of Hegel interpretation have so often revolved around the main philosophical, political and religious issues of the nineteenth and twentieth centuries, Hegelianism has also had a significant impact on the development of modern Western thought in its own right. As a result of its complex evolution, Hegelianism is best understood historically, by showing how the changing representation of Hegel’s ideas have come about, shaped by the different critical concerns, sociopolitical conditions and intellectual movements that dominated his reception in different countries at different times. Initially, Hegel’s influence was naturally most strongly felt in Germany as a comprehensive, integrative philosophy that seemed to do justice to all realms of experience and promised to preserve the Christian heritage in a modern and progressive form within a speculative framework. However, this position was quickly challenged, both from other philosophical standpoints (such as F.W.J. Schelling’s ‘positive philosophy’ and F.A. Trendelenburg’s neo-Aristotelian empiricism), and by the celebrated generation of younger thinkers (the so-called ‘Young’ or ‘Left’ Hegelians, such as Ludwig Feuerbach, David Strauss, Bruno Bauer, Arnold Ruge and the early Karl Marx), who insisted that to discover what made Hegel a truly significant thinker (his dialectical method, his view of alienation, his ‘sublation’ of Christianity), this orthodoxy must be overturned. None the less, both among these radicals and in academic circles, Hegel’s influence was considerably weakened in Germany by the 1860s and 1870s, while by this time developments in Hegelian thought had begun to take place elsewhere. Hegel’s work was known outside Germany from the 1820s onwards, and Hegelian schools developed in northern Europe, Italy, France, Eastern Europe, America and (somewhat later) Britain, each with their own distinctive line of interpretation, but all fairly uncritical in their attempts to assimilate his ideas. However, in each of these countries challenges to the Hegelian position were quick to arise, partly because the influence of Hegel’s German critics soon spread abroad, and partly because of the growing impact of other philosophical positions (such as Neo-Kantianism, materialism and pragmatism). Nevertheless, Hegelianism outside Germany proved more durable in the face of these attacks, as new readings and approaches emerged to counter them, and ways were found to reinterpret Hegel’s work to show that it could accommodate these other positions, once the earlier accounts of Hegel’s metaphysics, political philosophy and philosophy of religion (in particular) were rejected as too crude. This pattern has continued into the twentieth century, as many of the movements that began by defining themselves against Hegel (such as Neo-Kantianism, Marxism, existentialism, pragmatism, post-structuralism and even ‘analytic’ philosophy) have then come to find unexpected common ground, giving a new impetus and depth to Hegelianism as it began to be assimilated within and influenced by these diverse approaches. Such efforts at rapprochement began in the early part of the century with Wilhelm Dilthey’s attempt to link Hegel with his own historicism, and although they were more ambivalent, this connection was reinforced in Italy by Benedetto Croce and Giovanni Gentile. The realignment continued in France in the 1930s, as Jean Wahl brought out the more existentialist themes in Hegel’s thought, followed in the 1940s by Alexander Kojève’s influential Marxist readings. Hegelianism has also had an impact on Western Marxism through the writings of the Hungarian Georg Lukács, and this influence has continued in the critical reinterpretations offered by members of the Frankfurt School, particularly Theodor W. Adorno, Max Horkheimer, Herbert Marcuse, Jürgen Habermas and others. More recently, most of the major schools of philosophical thought (from French post-structuralism to Anglo-American ‘analytic’ philosophy) have emphasized the need to take account of Hegel, and as a result Hegelian thought (both exegetical and constructive) is continually finding new directions.


2010 ◽  
Vol 112 (6) ◽  
pp. 1301-1307 ◽  
Author(s):  
Chandan G. Reddy ◽  
Nader S. Dahdaleh ◽  
Gregory Albert ◽  
Fangxiang Chen ◽  
Daniel Hansen ◽  
...  

A wide range of devices is used to obtain intracranial electrocorticography recordings in patients with medically refractory epilepsy, including subdural strip and grid electrodes and depth electrodes. Penetrating depth electrodes are required to access some brain regions, and 1 target site that presents a particular technical challenge is the first transverse temporal gyrus, or Heschl gyrus (HG). The HG is located within the supratemporal plane and has an oblique orientation relative to the sagittal and coronal planes. Large and small branches of the middle cerebral artery abut the pial surface of the HG and must be avoided when planning the electrode trajectory. Auditory cortex is located within the HG, and there are functional connections between this dorsal temporal lobe region and medial sites commonly implicated in the pathophysiology of temporal lobe epilepsy. At some surgical centers, depth electrodes are routinely placed within the supratemporal plane, and the HG, in patients who require intracranial electrocorticography monitoring for presumed temporal lobe epilepsy. Information from these recordings is reported to facilitate the identification of seizure patterns in patients with or without auditory auras. To date, only one implantation method has been reported to be safe and effective for placing HG electrodes in a large series of patients undergoing epilepsy surgery. This well-established approach involves inserting the electrodes from a lateral trajectory while using stereoscopic stereotactic angiography to avoid vascular injury. In this report, the authors describe an alternative method for implantation. They use frameless stereotaxy and an oblique insertion trajectory that does not require angiography and allows for the simultaneous placement of subdural grid arrays. Results in 19 patients demonstrate the safety and efficacy of the method.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A439-A439
Author(s):  
Emi Ishida ◽  
Xiao Lei ◽  
Kazuhiko Horiguchi ◽  
Shunichi Matsumoto ◽  
Satoshi Yoshino ◽  
...  

Abstract In type 2 diabetes, pancreatic beta cells are gradually ‘exhausted’ and fall into beta cell dysfunction, which proceeds more severe insulin dependence. Among the proposed mechanisms of beta cell dysfunction such as endoplasmic reticulum stress and oxidative stress, the beta cell heterogeneity has attracted the researcher’s interest recently. In 2012, Talchai et al. revealed that the beta cells were dedifferentiated in diabetic mice model, and nowadays it is considered as one form of the beta cell heterogeneity and is observed broadly among diabetic animal models and human patients. Previously we showed that food restriction had the best effect to restore beta cell gene expression in obese diabetic model mice, among the known diabetic treatments which we tested. In the current study, we aimed to unveil the molecular basis in the improvement of beta cell dedifferentiation during the calorie restriction. First, we utilized the high-fat/low carbohydrate diet (HF) or low-fat/high carbohydrate (HC) diet, to determine whether fat restriction or sugar restriction reduces the beta cell dedifferentiation in obese mice. When calorie intake was restricted evenly, both HF diet and HC diet decreased the body weight and hyperglycemia in db/db mice equally. Albeit the same metabolic profile, db/db group fed with HC diet had more enlarged islets and more dedifferentiated beta cell features than db/dbs fed with HF diet, which indicated the compensatory beta cell response in HC diet group. Moreover, HC diet group showed more severe fatty liver than HF diet group, along with the elevated synthesis and accumulation of triglycerides and cholesterol in liver. It is speculated that the insulin resistance in liver might impact on the beta cell dedifferentiation. Next, we analyzed the effect of glucagon-like peptide 1 (GLP-1) on beta cell dedifferentiation, since GLP-1 is secreted more from intestine by protein and fat intake, rather than by sugar intake. Also, increasing number of reports have suggested the improving effect of GLP-1 on beta cell dysfunction and fatty liver. Indeed, GLP-1 administration altered the reduced beta cell/alpha cell ratio in db/db mice, which indicated the restoration of beta cell heterogeneity. We are now investigating if GLP-1 administration reimburse the beta cell dedifferentiation in db/db mice fed with HC diet, to illuminate the role of incretins in beta cell dedifferentiation induced by unbalanced nutrition during diet. Also, we will present the RNA sequencing data of the liver in db/db mice fed with HF and HC diet, to elucidate the key molecules and genes which connect the beta cell function and metabolic state in liver.


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