Glycosphingolipids and Insulin Resistance

Aerts, Johannes M. F. G.; Boot, Rolf G.; Eijk, Marco van; Groener, J.E.M.; Bijl, Nora; Lombardo, Elisa; Bietrix, Florence; Dekker, Natashe Lemos; Groen, Albert K.; Ottenhoff, Roelof; Roomen, Cindy van; Aten, Jan; Serlie, Mireille J.; Langeveld, Mirjam; Wennekes, Tom; Overkleeft, Hermen S.

doi:10.1007/978-1-4614-0650-1_7

Cited by 54 publications

(46 citation statements)

References 144 publications

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“…GSLs are membrane components that act as a secondary messengers and/or modulators of signal transduction by affecting numerous cellular events, such as cell homeostasis, cell adhesion, cell growth, cell motility, apoptosis, cell cycle, cell proliferation, differentiation, angiogenesis, stress, and inflammatory responses (4,5,44,46,52,65,69,130,151). GSLs functions are linked to various aspects of cancer, i.e., tumor growth, neoangiogenesis, and response to chemotherapy (5,12,44,46,54).…”

Section: Sphingolipid Steady State In Health and Diseasementioning

confidence: 99%

“…A regulatory interaction of GSLs with insulin signaling has been demonstrated (4,5,31). The insulin receptor is localized at the cell surface in a GSL-containing lipid microdomain (32,93,97).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…Both Cer and GC are minor components of the lipid milieu in most tissues and they are potential pathogenic lipids in several conditions, including states of excess adiposity (24,25,33,34,75,79). GSLs are structural membrane components located mainly in the plasma membrane, with their sugar moieties exposed at the cell surface (4,5,31). Cer, GC, and GM3 modify several steps of the insulin signaling pathway, such as phosphorylation with Akt or the insulin receptor (35,135,139).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

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Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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The compounds of sphingomyelin-ceramide-glycosphingolipid pathways have been studied as potential secondary messenger molecules in various systems, along with liver function and insulin resistance. Secondary messenger molecules act directly or indirectly to affect cell organelles and intercellular interactions. Their potential role in the pathogenesis of steatohepatitis and diabetes has been suggested. Data samples collected from patients with Gaucher's disease, who had high levels of glucocerebroside, support a role for compounds from these pathways as a messenger molecules in the pathogenesis of fatty liver disease and diabetes. The present review summarizes some of the recent data on the role of glycosphingolipid molecules as messenger molecules in various physiological and pathological conditions, more specifically including insulin resistance and fatty liver disease.

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Section: Sphingolipid Steady State In Health and Diseasementioning

confidence: 99%

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

See 1 more Smart Citation

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…(46) Glycosphingolipid accumulation has been associated with insulin resistance. (47) In GD1, glycosphingolipid accumulation is also associated with abnormal cholesterol metabolism (48) and non-obesity dependent decreases in serum adiponectin levels. (49) It is hypothesized by Youm and colleagues (43) that abnormalities in blood cholesterol and triglyceride levels, sometimes associated with alcohol consumption, may be associated with nontraumatic osteonecrosis of the femoral head.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

Khan

Hangartner

Weinreb³

et al. 2012

Journal of Bone and Mineral Research

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We hypothesized that overall disease activity or the severity of involvement of individual disease compartments, as measured by clinical and surrogate markers, predict the risk of avascular osteonecrosis (AVN) or fractures in type 1 Gaucher disease (GD1). We applied our risk‐set matched case‐control method to identify four patient groups within the International Collaborative Gaucher Group (ICGG) Gaucher Registry based on the presence and absence of AVN and fractures. Characteristics of GD1 were examined by comparing the distributions of each risk factor in cases versus matched controls using conditional logistic regression to calculate adjusted odds ratios (OR). Potential risk factors included hematological and visceral parameters, GD1 biomarkers, white blood cells, GBA1 genotype, and spine and femur dual‐energy X‐ray absorptiometry (DXA) Z‐scores. In the total population of 5894 ICGG Gaucher Registry patients, 544 experienced at least one episode of AVN; 2008 reported no history of AVN. Clinical and surrogate markers of disease activity were similar in patients with and without AVN; patients with AVN were 1.6 times more likely to be anemic compared to matched controls (OR = 1.59; 95% confidence interval [CI], 1.06–2.38, p < 0.05). For fractures, 319 patients suffered fractures and 1233 had no prior history of fractures. Clinical and surrogate markers of disease in patients with and without fractures were similar, except for mean lumbar spine DXA Z‐scores. Among patients with fractures, 49.3% had DXA Z‐scores ≤ −1 compared to 31.0% in the control group. Compared to controls with Z‐scores > −1.0, GD1 patients exhibiting Z‐scores ≤ −1 had an OR of 5.55 (95% CI, 1.81–17.02, p < 0.01) for fracture. In GD1, after controlling for gender, year of birth, treatment status, and splenectomy status, we identified new risk factors for AVN and fractures. Concurrent anemia was associated with an increased risk for AVN. Low bone mineral density of the lumbar spine was a strong risk factor for fractures of the spine and femur in GD1. © 2012 American Society for Bone and Mineral Research.

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“…2). En la actualidad existe controversia sobre la importancia del papel que desempeñan las ceramidas en la resistencia a la insulina, debido a las diferencias en los resultados obtenidos: en algunos estudios se ha encontrado una correlación directa entre la acumulación de ceramidas y la resistencia a la insulina, pero en otros se sugiere que los AGS promueven resistencia a la insulina por el incremento en las concentraciones de DAG, sin cambios significativos en el contenido de ceramidas 32,33 .…”

Section: Ceramidas Y Resistencia a La Insulinaunclassified