The glycolipid sulfatide protects insulin‐producing cells against cytokine‐induced apoptosis, a possible role in diabetes

Roeske-Nielsen, Allan; Dalgaard, Louise Torp; Månsson, Jan‐Eric; Buschard, Karsten

doi:10.1002/dmrr.1130

Cited by 13 publications

(11 citation statements)

References 47 publications

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“…For example, administration of C16:0-sulfatide, specifically, to Zucker fatty rats, which express a defective leptin receptor, reduced fasting insulin and improved the first-phase insulin response and glucose-stimulated insulin response (Blomqvist et al 2005). More generally, sulfatide was shown to protect isolated islet cells from apoptosis, iNOS expression, and nitric oxide secretion induced by cytokines; this protective effect was not specific to C16:0-sulfatide (Roeske-Nielsen et al 2010). These findings indicate that sulfatide exerts a protective effect in pancreatic islets via normalization of insulin secretion and protection from inflammation.…”

Section: Sphingolipids In the Diabetic Pancreasmentioning

confidence: 99%

Sphingolipids in Obesity, Type 2 Diabetes, and Metabolic Disease

Russo

Ross

Cowart

2013

Handbook of Experimental Pharmacology

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Metabolic disease, including obesity and type 2 diabetes, constitutes a major emerging health crisis in Western nations. Although the symptoms and clinical pathology and physiology of these conditions are well understood, the molecular mechanisms underlying the disease process have largely remained obscure. Sphingolipids, a lipid class with both signaling and structural properties, have recently emerged as key players in most major tissues affected by diabetes and are required components in the molecular etiology of this disease. Indeed, sphingolipids have been shown to mediate loss of insulin sensitivity, to promote the characteristic diabetic pro-inflammatory state, and to induce cell death and dysfunction in important organs such as the pancreas and heart. Furthermore, plasma sphingolipid levels are emerging as potential biomarkers for the decompensation of insulin resistance to frank type 2 diabetes. Despite these discoveries, the roles of specific sphingolipid species and sphingolipid metabolic pathways remain obscure, and newly developed experimental approaches must be employed to elucidate the detailed molecular mechanisms necessary for rational drug development and other clinical applications.

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Section: Sphingolipids In the Diabetic Pancreasmentioning

confidence: 99%

Sphingolipids in Obesity, Type 2 Diabetes, and Metabolic Disease

Russo

Ross

Cowart

2013

Handbook of Experimental Pharmacology

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“…Although proinflammatory cytokines have been implicated in apoptosis of nucleated cells (Roeske-Nielsen et al 2010), their pro-apoptotic effects were not observed when fresh or pRBCs were maintained in the presence of TNF and/or IL-1 (Pattanapanyasat et al 2010). Our results are also in accordance with the possible refractoriness of RBCs to cytokine-induced apoptosis (Neote et al 1994, Daniels 2007) because IFN-γ levels were elevated at stages of infection that were related (late stage) and not related (early stage) to nRBC apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis of non-parasitised red blood cells in Plasmodium yoelii malaria

Totino

Pinna

De-Oliveira

et al. 2013

Mem. Inst. Oswaldo Cruz

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Recently, while studying erythrocytic apoptosis during Plasmodium yoelii infection, we observed an increase in the levels of non-parasitised red blood cell (nRBC) apoptosis, which could be related to malarial anaemia. Therefore, in the present study, we attempted to investigate whether nRBC apoptosis is associated with the peripheral RBC count, parasite load or immune response. To this end, BALB/c mice were infected with P. yoelii 17XL and nRBC apoptosis, number of peripheral RBCs, parasitaemia and plasmatic levels of cytokines, nitric oxide and anti-RBC antibodies were evaluated at the early and late stages of anaemia. The apoptosis of nRBCs increased at the late stage and was associated with parasitaemia, but not with the intensity of the immune response. The increased percentage of nRBC apoptosis that was observed when anaemia was accentuated was not related to a reduction in peripheral RBCs. We conclude that nRBC apoptosis in P. yoelii malaria appears to be induced in response to a high parasite load. Further studies on malaria models in which acute anaemia develops during low parasitaemia are needed to identify the potential pathogenic role of nRBC apoptosis.

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“…Insulin is a key autoantigen in type 1 diabetes, giving rise to both anti-insulin autoantibodies and T cell autoreactivity in preclinical models and new-onset patients [38], [39]. Sulfatide protects insulin-producing cells from cytokine-induced apoptosis [40] and increased insulin production together with reduced sulfatide expression may be an unfortunate combination negatively affecting local immune homeostasis and, hence, may serve as an important checkpoint in the pathogenesis of type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Self-Glycolipids Modulate Dendritic Cells Changing the Cytokine Profiles of Committed Autoreactive T Cells

et al. 2012

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The impact of glycolipids of non-mammalian origin on autoimmune inflammation has become widely recognized. Here we report that the naturally occurring mammalian glycolipids, sulfatide and β-GalCer, affect the differentiation and the quality of antigen presentation by monocyte-derived dendritic cells (DCs). In response to sulfatide and β-GalCer, monocytes develop into immature DCs with higher expression of HLA-DR and CD86 but lower expression of CD80, CD40 and CD1a and lower production of IL-12 compared to non-modulated DCs. Self-glycolipid-modulated DCs responded to lipopolysaccharide (LPS) by changing phenotype but preserved low IL-12 production. Sulfatide, in particular, reduced the capacity of DCs to stimulate autoreactive Glutamic Acid Decarboxylase (GAD65) - specific T cell response and promoted IL-10 production by the GAD65-specific clone. Since sulfatide and β-GalCer induced toll-like receptor (TLR)-mediated signaling, we hypothesize that self-glycolipids deliver a (tolerogenic) polarizing signal to differentiating DCs, facilitating the maintenance of self-tolerance under proinflammatory conditions.

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The glycolipid sulfatide protects insulin‐producing cells against cytokine‐induced apoptosis, a possible role in diabetes

Cited by 13 publications

References 47 publications

Sphingolipids in Obesity, Type 2 Diabetes, and Metabolic Disease

Sphingolipids in Obesity, Type 2 Diabetes, and Metabolic Disease

Apoptosis of non-parasitised red blood cells in Plasmodium yoelii malaria

Self-Glycolipids Modulate Dendritic Cells Changing the Cytokine Profiles of Committed Autoreactive T Cells

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