A Holistic View of the Goto-Kakizaki Rat Immune System: Decreased Circulating Immune Markers in Non- Obese Type 2 Diabetes

Type-2 diabetes is a complex disorder that is now considered to have an immune component, with functional impairments in many immune cell types. Type-2 diabetes is often accompanied by comorbid obesity, which is associated with low grade inflammation. However,the immune status in Type-2 diabetes independent of obesity remains unclear. Goto-Kakizaki rats are a non-obese Type-2 diabetes model. The limited evidence available suggests that Goto-Kakizaki rats have a pro-inflammatory immune profile in pancreatic islets. Here we present a detailed overview of the adult Goto-Kakizaki rat immune system. Three converging lines of evidence: fewer pro-inflammatory cells, lower levels of circulating pro-inflammatory cytokines, and a clear downregulation of pro-inflammatory signalling in liver, muscle and adipose tissues indicate a limited pro-inflammatory baseline immune profile outside the pancreas. As Type-2 diabetes is frequently associated with obesity and adipocyte-released inflammatory mediators, the pro-inflammatory milieu seems not due to Type-2 diabetes per se; although this overall reduction of immune markers suggests marked immune dysfunction in Goto-Kakizaki rats. Copyright © 2022 Seal, Henry, Pajot, Holuka, Bailbé, Movassat, Darnaudéry and Turner.Diabète maternel et vulnérabilité neuropsychiatrique chez la descendance : rôle de la méthylation de l'AD

Impaired mitochondrial oxidative response to D-glucose in islets from streptozotocin-injected rats

info:eu-repo/semantics/publishedComm. 26th Annual Meeting of the European Association for the Study of Diabetes - Copenhagen, 10.09.199

Impairment of the mitochondrial oxidative response to D-glucose in pancreatic islets from adult rats injected with streptozotocin during the neonatal period

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Metabolic, ionic and secretory response to D-glucose in islets from rats with acquired or inherited non-insulin-dependent diabetes

info:eu-repo/semantics/publishe

Study of hexose transport, glycerol phosphate shuttle and Krebs cycle in islets of adult rats injected with streptozotocin during the neonatal period

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Metabolic response to nonglucidic nutrient secretagogues and enzymatic activities in pancreatic islets of adult rats after neonatal streptozotocin administration

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Metabolic response to non-glucidic nutrient secretagogues in pancreatic islets of adult rats after neonatal streptozotocin administration

info:eu-repo/semantics/publishedComm. Symposium on Islet Metabolism and Physiopathology - Istanbul (Turkey), 11.09.199

Metabolic response to non-glucidic nutrient secretagogues and enzymic activities in pancreatic islets of adult rats after neonatal streptozotocin administration

info:eu-repo/semantics/publishe

Underlying mechanisms of glucocorticoid-induced beta-cell death and dysfunction: a new role for glycogen synthase kinase 3

International audienceGlucocorticoids (GCs) are widely prescribed for their anti-inflammatory and immunosuppressive properties as a treatment for a variety of diseases. The use of GCs is associated with important side effects, including diabetogenic effects. However, the underlying mechanisms of GC-mediated diabetogenic effects in beta-cells are not well understood. In this study we investigated the role of glycogen synthase kinase 3 (GSK3) in the mediation of beta-cell death and dysfunction induced by GCs. Using genetic and pharmacological approaches we showed that GSK3 is involved in GC-induced beta-cell death and impaired insulin secretion. Further, we unraveled the underlying mechanisms of GC-GSK3 crosstalk. We showed that GSK3 is marginally implicated in the nuclear localization of GC receptor (GR) upon ligand binding. Furthermore, we showed that GSK3 regulates the expression of GR at mRNA and protein levels. Finally, we dissected the proper contribution of each GSK3 isoform and showed that GSK3 beta isoform is sufficient to mediate the pro-apoptotic effects of GCs in beta-cells. Collectively, in this work we identified GSK3 as a viable target to mitigate GC deleterious effects in pancreatic beta-cells