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Titre : | Direct role of IL-1 alpha on pancreatic islet function. |
Auteurs : | Alessia Romanin, Auteur ; Leticia Prates Roma, Promoteur |
Type de document : | Travail de fin d'études |
Editeur : | Woluwe-Saint-Lambert : Haute École Léonard de Vinci, 2022 |
Langues: | Anglais |
Index. décimale : | TFE - Biologie médicale |
Descripteurs : |
HE Vinci Cytokines ; Ilots pancréatiques ; Insuffisance rénale chronique ; Interleukines ; Sécrétion d'insuline ; Souris |
Mots-clés: | Interleukine-1 alpha ; ROS production ; Ca 2+ ; Beta-cells |
Résumé : |
Interleukin 1 (IL-1) was discovered in the 1970s [1]. Since then, scientific studies have focused on the roles, effects, and functions of these proinflammatory cytokines on the human body. The main role of the Interleukin-1 family members is a function in the immunity and inflammation [4]. Although the effects of many cytokines, such as IL-1 β, TNF, INF y, have already been studied in more details, many roles remain to be clarified concerning these cytokines [21]. During my thesis, I will mainly develop the roles of IL-1 α on the islets of Langerhans, clusters of thousands of hormone-secreting endocrine cells, located in the pancreas [1,2]. The starting point of this research was the discovery of a direct link between Interleukin-1 α secretion and chronic kidney disease (CKD). Indeed, as a result, we can highlight that IL-1 α is strongly expressed on the surface of immune cells from patients who are suffering from stable CKD compared with healthy subjects [6]. The main issue is that higher expression of IL-1 α on the surface of immune cells is associated with a higher risk for cardiovascular diseases(CVD) [6]. But, if it is already known that IL 1 α has an adverse effect on the heart, what are the effects on pancreatic islets? During my thesis, I will show that IL-1 α has a crucial effect on glucose-stimulated insulin secretion (GSIS). Indeed IL-1 α appears to have a double effect on GSIS: potentiation and inhibition. All this depends on the parameters of IL-1 α concentrations and the incubation time of the islets with this cytokine [12,13]. In lowglucose condition (2.8 mM) and in long time incubation (18 h), the concentration of IL-1 α seem does not seem to influence the insulin secretion. On the other hand, in high-glucose condition (20 mM) and in long time incubation, inhibition of GSIS was observed. As results, we can clearly see an implication of cytokines in β-cell
failures and mainly on GSIS dysfunctions. Next to the question of GSIS, this thesis investigates the net calcium (Ca2+) uptake into pancreatic islets exposed to different concentrations of IL-1 α. By this way, the impacts of IL-1 α on the quality of Ca2+ uptake into a pancreatic cell were analyzed with a microplate reader. Because one of the main steps for insulin secretion from β-cells is the Ca 2+ influx upon glucose exposure, it is crucial to know if this proinflammatory cytokine has a role in the Ca 2+ uptake [20]. After exposing pancreatic islets isolated from mice to different concentrations of IL-1 α, we can clearly see that the net Ca2+ uptake decreases under exposure to IL-1 α. Thus, we can maybe explain the decrease in insulin secretion in pancreatic islets with presence of IL-1 α because of the decrease in net Ca2+ uptake that is vital in pancreatic β-cells due to its importance in the process of insulin release [16]. Finally, aerobic organisms use inevitably molecular oxygen to accomplish their actions. This utilization results in the formation of reactive oxygen species (ROS). These ROS play crucial roles in both physiology and pathophysiology of aerobic life [36]. Because ROS production in β-cells is ones of the key regulators of GSIS, the levels of H2O2 in mitochondrial matrix and cytosol/nucleus were measured with a genetically encoded sensor [37,21]. One of the major free radical produces by our cells, during the respiratory chain in mitochondria, is the superoxide anion radical (O2·−). This O2·− is quickly converted in hydrogen peroxide (H2O2) [25]. My experiments highlight that H2O2 levels are increased in both compartments in presence of IL-1 α. Thus, have shown that some proinflammatory cytokines have an impact on ROS production by pancreatic islets. Indeed, when pancreatic islets are exposed to some proinflammatory cytokines, that lead, among other things, to an excessive generation of ROS by the pancreatic islets and consequently to oxidative stress [21]. ROS, in non-physiological conditions, have been associated with β-cells dysfunctions and sometimes until the death of these cells [21]. By measuring the H2O2 levels under IL-1 α exposure and would indicate whether this cytokine influences the production of H2O2. |
Accès : | Identifiez-vous avant d'accéder au document électronique |
Disponible en ligne : | Oui |
Lieu du stage : | CIPMM (Center for Integrative Physiology and Molecular Medicine), Homburg, Allemagne |
Département : | Biologie médicale |
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