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

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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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

The Role of α-Cells in Islet Function and Glucose Homeostasis in Health and Type 2 Diabetes.

Pancreatic α-cells are the major source of glucagon, a hormone that counteracts the hypoglycemic action of insulin and strongly contributes to the correction of acute hypoglycemia. The mechanisms by which glucose controls glucagon secretion are hotly debated, and it is still unclear to what extent this control results from a direct action of glucose on α-cells or is indirectly mediated by β- and/or δ-cells. Besides its hyperglycemic action, glucagon has many other effects, in particular on lipid and amino acid metabolism. Counterintuitively, glucagon seems also required for an optimal insulin secretion in response to glucose by acting on its cognate receptor and, even more importantly, on GLP-1 receptors. Patients with diabetes mellitus display two main alterations of glucagon secretion: a relative hyperglucagonemia that aggravates hyperglycemia, and an impaired glucagon response to hypoglycemia. Under metabolic stress states, such as diabetes, pancreatic α-cells also secrete GLP-1, a glucose-lowering hormone, whereas the gut can produce glucagon. The contribution of extrapancreatic glucagon to the abnormal glucose homeostasis is unclear. Here, I review the possible mechanisms of control of glucagon secretion and the role of α-cells on islet function in healthy state. I discuss the possible causes of the abnormal glucagonemia in diabetes, with particular emphasis on type 2 diabetes, and I briefly comment the current antidiabetic therapies affecting α-cells