Vivre ensemble dans un monde médiatisé: parcours pédagogiques pour les 2e et 3e degrés de l’enseignement secondaire

Les événements dramatiques qui ont marqué l’année 2015, tant en Europe qu’au Moyen Orient et en Afrique, engendrent de nombreux défis pédagogiques pour les enseignants. Face aux émotions et aux réactions des élèves, parfois sensibles à la propension à la haine dans certains discours médiatiques et politiques, comment traiter les notions fondamentales qui forment les piliers de nos sociétés démocratiques ? Cet ouvrage collectif, fruit du travail d’une trentaine de chercheurs et de professionnels de l’éducation, entend proposer des supports pour conduire des réflexions en classe autour de la liberté de pensée et de culte, la liberté de la presse, la laïcité, l’esprit critique et l’égalité de traitement des individus. Cet ouvrage a été construit autour du croisement entre une approche centrée sur l’éducation aux médias et une approche philosophique. Chacune de ces approches est organisée autour de dix thématiques. Celles-ci sont présentées sous forme d’un court article de réflexion et de vulgarisation et sont soutenues par une fiche pédagogique destinée à l’enseignant qui reprend le canevas d’une proposition de cours. Un « document-élève » est téléchargeable sur le site Internet du Conseil supérieur d’éducation aux médias (www.csem.be/vivreensemble). Il peut être directement utilisé en classe et est personnalisable par l’enseignant. Cette publication est dense et multiple. Elle permet à l’enseignant, tant de l’enseignement général que qualifiant, de s’approprier chacune des thématiques de manière réflexive mais aussi très concrète et didactique. Chacun y trouvera une entrée spécifique qui le conduira vers d’autres approches. Les croisements possibles entre différentes fiches permettent de revenir sur certains débats de nos sociétés contemporaines : construction du vivre-ensemble, approche citoyenne des médias, multi-culturalité et identité plurielle, embrigadement et fanatisation des jeunes, etc

Glucose and Pharmacological Modulators of ATP-Sensitive K+ Channels Control [Ca2+]c by Different Mechanisms in Isolated Mouse α-Cells

OBJECTIVE—We studied how glucose and ATP-sensitive K+ (KATP) channel modulators affect α-cell [Ca2+]c

LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes

The lactate dehydrogenase isoform A (LDHA) is a key metabolic enzyme that preferentially catalyzes the conversion of pyruvate to lactate. Whereas LDHA is highly expressed in many tissues, its expression is turned off in the differentiated adult β-cell within the pancreatic islets. The repression of LDHA under normal physiological condition and its inappropriate upregulation under a diabetogenic environment is well-documented in rodent islets/β-cells but little is known about LDHA expression in human islet cells and whether its abundance is altered under diabetic conditions. Analysis of public single-cell RNA-seq (sc-RNA seq) data as well as cell type-specific immunolabeling of human pancreatic islets showed that LDHA was mainly localized in human α-cells while it is expressed at a very low level in β-cells. Furthermore, LDHA, both at mRNA and protein, as well as lactate production is upregulated in human pancreatic islets exposed to chronic high glucose treatment. Microscopic analysis of stressed human islets and autopsy pancreases from individuals with type 2 diabetes (T2D) showed LDHA upregulation mainly in human α-cells. Pharmacological inhibition of LDHA in isolated human islets enhanced insulin secretion under physiological conditions but did not significantly correct the deregulated secretion of insulin or glucagon under diabetic conditions

The GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner

© 2024, [BioScientifica]. This is an author produced version of a paper published in Journal of Endocrinology uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it. LEAP2, a liver-derived antagonist for theghrelin receptor, GHSR1a, counteracts effects of ghrelin on appetite and energybalance. Less is known about its impact on blood glucose-regulating hormonesfrom pancreatic islets. Here we investigate whether acyl-ghrelin (AG) and LEAP2regulate islet hormone release in a cell type- and sex-specific manner. Hormonecontent from secretion experiments with isolated islets from male and femalemice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2enhanced insulin secretion in islets from males (p<0.01) but not females(p>0.2), whilst AG-stimulated somatostatin release was significantlyreversed by LEAP2 in males (p<0.001) but not females (p>0.2). Glucagonrelease was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin,Leap2, Mrap2, Mboat4 and Sstr3 islet mRNA expression did notdiffer between sexes whereas the SSTR3 antagonist MK4256 enhanced glucose-induced insulin secretion in islets from males only. In control male islets maintained without 17-betaoestradiol (E2),AG exerted an insulinostatic effect (p<0.05), with a trend towards reversalby LEAP2 (p=0.06). Both were abolished by 72h E2 pre-treatment (10 nmol/l,p>0.2). AG-stimulated somatostatin release was inhibited by LEAP2 fromcontrol (p<0.001) but not E2-treated islets (p>0.2). LEAP2and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2was downregulated (P<0.05) and Ghsr1a upregulated (P<0.0001) inislets from Sst-/- mice. Our findings show that AG and LEAP2regulate insulin and somatostatin release in an opposing and sex-dependentmanner, which in males can be modulated by E2. We suggest that regulation ofSST release is a key starting point for understanding the role of GHSR1a inislet function and glucose metabolism.

UCP2 Regulates the Glucagon Response to Fasting and Starvation

Glucagon is important for maintaining euglycemia during fasting/starvation, and abnormal glucagon secretion is associated with type 1 and type 2 diabetes; however, the mechanisms of hypoglycemia-induced glucagon secretion are poorly understood. We previously demonstrated that global deletion of mitochondrial uncoupling protein 2 (UCP2−/−) in mice impaired glucagon secretion from isolated islets. Therefore, UCP2 may contribute to the regulation of hypoglycemia-induced glucagon secretion, which is supported by our current finding that UCP2 expression is increased in nutrient-deprived murine and human islets. Further to this, we created α-cell–specific UCP2 knockout (UCP2AKO) mice, which we used to demonstrate that blood glucose recovery in response to hypoglycemia is impaired owing to attenuated glucagon secretion. UCP2-deleted α-cells have higher levels of intracellular reactive oxygen species (ROS) due to enhanced mitochondrial coupling, which translated into defective stimulus/secretion coupling. The effects of UCP2 deletion were mimicked by the UCP2 inhibitor genipin on both murine and human islets and also by application of exogenous ROS, confirming that changes in oxidative status and electrical activity directly reduce glucagon secretion. Therefore, α-cell UCP2 deletion perturbs the fasting/hypoglycemic glucagon response and shows that UCP2 is necessary for normal α-cell glucose sensing and the maintenance of euglycemia

Acute type A aortic dissection in the elderly: clinical characteristics, management, and outcomes in the current era

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Differences in Clinical Presentation, Management, and Outcomes of Acute Type A Aortic Dissection in Patients With and Without Previous Cardiac Surgery

Background— There are less data on the clinical and diagnostic imaging characteristics, management, and outcomes of patients with previous cardiac surgery (PCS) presenting with acute type A aortic dissection (AAD). Methods and Results— In 617 patients with AAD, we evaluated the differences in the clinical characteristics, management, and in-hospital outcomes of the cohorts with and without PCS. A history of PCS was present in 100 of 617 patients. Patients with PCS were more likely to be males ( P =0.02), older ( P =0.014), and to have a history of previous aortic dissection ( P <0.001) or aneurysms ( P <0.001). In contrast, PCS patients were less likely to have presenting chest pain ( P <0.001). Cardiac tamponade was less common in PCS patients ( P =0.007). Fewer AAD patients with PCS underwent surgical repair ( P =0.001). Hospital mortality was not adversely influenced by PCS (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.81 to 2.63), but a trend for increased death was seen in patients with previous aortic valve replacement (AVR) (OR, 2.31; 95% CI, 0.98 to 5.43). Age70 years or older, previous AVR, shock, and renal failure identified PCS patients at risk for death. Conclusions— Our study highlights differences in clinical characteristics, management, and outcomes of AAD patients with PCS. Importantly, PCS, with the exception of previous AVR, does not adversely influence early outcomes of AAD patients, including those undergoing surgical repair. However, because of otherwise dismal outcomes with medical management of AAD, our data indicate that a history of PCS (even that of previous AVR) should not preclude physicians from recommending surgical correction of type A aortic dissection in appropriate patients

SGLT2 is not expressed in pancreatic α- and β-cells, and its inhibition does not directly affect glucagon and insulin secretion in rodents and humans.

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i), or gliflozins, are anti-diabetic drugs that lower glycemia by promoting glucosuria, but they also stimulate endogenous glucose and ketone body production. The likely causes of these metabolic responses are increased blood glucagon levels, and decreased blood insulin levels, but the mechanisms involved are hotly debated. This study verified whether or not SGLT2i affect glucagon and insulin secretion by a direct action on islet cells in three species, using multiple approaches. METHODS: We tested the in vivo effects of two selective SGLT2i (dapagliflozin, empagliflozin) and a SGLT1/2i (sotagliflozin) on various biological parameters (glucosuria, glycemia, glucagonemia, insulinemia) in mice. mRNA expression of SGLT2 and other glucose transporters was assessed in rat, mouse, and human FACS-purified α- and β-cells, and by analysis of two human islet cell transcriptomic datasets. Immunodetection of SGLT2 in pancreatic tissues was performed with a validated antibody. The effects of dapagliflozin, empagliflozin, and sotagliflozin on glucagon and insulin secretion were assessed using isolated rat, mouse and human islets and the in situ perfused mouse pancreas. Finally, we tested the long-term effect of SGLT2i on glucagon gene expression. RESULTS: SGLT2 inhibition in mice increased the plasma glucagon/insulin ratio in the fasted state, an effect correlated with a decline in glycemia. Gene expression analyses and immunodetections showed no SGLT2 mRNA or protein expression in rodent and human islet cells, but moderate SGLT1 mRNA expression in human α-cells. However, functional experiments on rat, mouse, and human (29 donors) islets and the in situ perfused mouse pancreas did not identify any direct effect of dapagliflozin, empagliflozin or sotagliflozin on glucagon and insulin secretion. SGLT2i did not affect glucagon gene expression in rat and human islets. CONCLUSIONS: The data indicate that the SGLT2i-induced increase of the plasma glucagon/insulin ratio in vivo does not result from a direct action of the gliflozins on islet cells

Oscillations, Intercellular Coupling, and Insulin Secretion in Pancreatic β Cells

Insulin is a potent metabolic regulator that is released by pancreatic beta-cells, which respond to body glucose concentrations. Here the authors explain the physiological basis of insulin release