M Cnop

..FRDA patients have a high prevalence of diabetes, the pathogenesis of which is not known. We aimed to evaluate the relative contribution of insulin resistance and β-cell failure and the pathogenic mechanisms involved in FRDA diabetes...

..This study elucidates the crosstalk between lipotoxic ER stress and the mitochondrial pathway of apoptosis that causes β-cell death in diabetes...

..Finally, prolonged ER stress impairs insulin synthesis and causes pancreatic β cell apoptosis. In this review, we discuss ways in which ER stress operates as a common molecular pathway in the pathogenesis of obesity and diabetes...

..Chemical chaperones, salubrinal and glucagon-like peptide-1 (GLP-1) analogues have been used to protect β-cells from lipotoxic ER stress. Importantly, the pro- and antiapoptotic effects of these compounds are cell and context dependent...

..In the present mini-review, we focus on recent progress in the field of ER stress in pancreatic beta-cells. Recent advances in the understanding of lipotoxic ER stress and beta-cell recovery from ER stress are discussed...

..A better understanding of the molecular mechanisms contributing to pancreatic beta-cell loss will pave the way for the development of novel and targeted approaches to prevent Type 2 diabetes...

..This modifies the present paradigm regarding the beneficial role of eIF2alpha phosphorylation in beta-cells and must be taken into consideration when designing therapies to protect beta-cells in type 2 diabetes...

..This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes...

..Our results argue against a unifying hypothesis for the mechanisms of beta-cell death in T1DM and T2DM...

..Induction of regeneration of human islet cells will require understanding of the mechanisms associated with age-related senescence...

..One of the proposed mechanisms of beta cell failure is local inflammation, but the presence of pancreatic islet inflammation in type 2 diabetes and the mechanisms involved remain under debate...

..This should be taken into consideration when designing approaches to pharmacologically modulate the beta-cell ER stress response in type 2 diabetes...

..It is conceivable that this potential is lost or insufficient in cells with a prolonged triglyceride accumulation as may occur in vivo...

..We hypothesized that PTPN2 plays a direct role in beta-cell demise and assessed PTPN2 expression in human islets and rat primary and clonal beta-cells, besides evaluating its role in cytokine-induced signaling and beta-cell apoptosis...

..These and other findings provide a first glimpse on how different signals trigger diverging UPR outcomes...

..A better understanding of the pathways regulating ER stress in beta-cells may be instrumental for the design of novel therapies to prevent beta-cell loss in diabetes...

..Here, we evaluated the molecular mechanisms involved in the protection of beta-cells from lipotoxic ER stress by glucagon-like peptide (GLP)-1 agonists utilized in the treatment of type 2 diabetes...

..In conclusion, saturated FFA induce ER stress via ER Ca(2+) depletion. The IRE1 and resulting JNK activation contribute to beta-cell apoptosis. PERK activation by palmitate also contributes to beta-cell apoptosis via CHOP...

..Regulated adiponectin receptor expression on pancreatic beta cells might be a novel mechanism modulating the effects of circulating adiponectin...

..PPAR-delta controls cellular lipid metabolism and is a major regulator of inflammatory responses. We therefore examined the role of PPAR-delta in cytokine-treated beta cells...

..Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1-81 years...

..The bioavailability of the developed formulations was within the range of other DPI insulin formulations that have reached the final stages of clinical development...

..Further understanding of these pathways may open new possibilities to improve β-cell survival in early type 1 diabetes or after transplantation...

..We suggest that neonatal hemochromatosis may be part of the Martinez-Frias syndrome. Molecular analyses in this and other reported patients with the Martinez-Frias syndrome should shed light on gut development and iron metabolism...

..These results suggest a differential response of beta-cells to diverse endoplasmic reticulum stress inducers, leading to a differential regulation of Chop transcription...

..This makes it unlikely that locally produced IL-1beta is an important mediator of glucotoxicity to human islets and argues against the IL-1beta-NF-kappaB-Fas pathway as a common mediator for beta-cell death in type 1 and type 2 diabetes...

..It is concluded that uptake of LDL by islet beta-cells and subsequent oxidative reactions can be damaging for the cells. This process can be counteracted by HDL and VLDL, and by antioxidants...

..They instead indicate that the agent may sensitize pancreatic beta cells to FFA-induced damage, raising the possibility that its use facilitates the deleterious effect of increased FFA levels on the pancreatic beta cell mass...

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..We provide molecular evidence in vivo demonstrating that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a PPARgamma-dependent mechanism...

..Both insulin resistance and impaired beta-cell function are associated with impaired glucose metabolism in all ethnic groups, with beta-cell function seeming to be more important in determining glucose disposal...

..Thus an atherogenic lipoprotein profile appears to be the result primarily of an increase in IAF, perhaps via insulin resistance...

..First-degree relatives of individuals with type 2 diabetes are at increased risk of developing hyperglycemia...