Glycosphingolipids and insulin resistance.

Abstract

Glycosphingolipids are structural membrane components, residing largely in the plasma membrane with their sugar-moieties exposed at the cell's surface. In recent times a crucial role for glycosphingolipids in insulin resistance has been proposed. A chronic state of insulin resistance is a rapidly increasing disease condition in Western and developing countries. It is considered to be the major underlying cause of the metabolic syndrome, a combination of metabolic abnormalities that increases the risk for an individual to develop Type 2 diabetes, obesity, cardiovascular disease, polycystic ovary syndrome and nonalcoholic fatty liver disease. As discussed in this chapter, the evidence for a direct regulatory interaction of glycosphingolipids with insulin signaling is still largely indirect. However, the recent finding in animal models that pharmacological reduction of glycosphingolipid biosynthesis ameliorates insulin resistance and prevents some manifestations of metabolic syndrome, supports the view that somehow glycosphingolipids act as critical regulators, Importantly, since reductions in glycosphingolipid biosynthesis have been found to be well tolerated, such approaches may have a therapeutic potential.

• Authors: Johannes M Aerts, Rolf G Boot, Marco van Eijk, Johanna Groener, Nora Bijl, Elisa Lombardo, Florence M Bietrix, Nick Dekker, Albert K Groen, Roelof Ottenhoff, Cindy van Roomen, Jan Aten, Mireille Serlie, Mirjam Langeveld, Tom Wennekes, Hermen S Overkleeft
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 721 Pg. 99-119 ( 2011) ISSN: 0065-2598 [Print] United States
• PMID: 21910085 (Publication Type: Journal Article, Review)

Chemical References

• (2-(2',3'-dihydrobenzo(1,4)dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethylethyl)nonanoic acid amide
• Ceramides
• Dioxanes
• Fatty Acids
• Glycosphingolipids
• N-(5-adamantane-1-yl-methoxy-pentyl)deoxynojirimycin
• Pyrrolidines
• 1-Deoxynojirimycin
• Glucosyltransferases
• ceramide glucosyltransferase
• Receptor, Insulin
• Adamantane

Topics

• 1-Deoxynojirimycin (analogs & derivatives, therapeutic use)
• Adamantane (analogs & derivatives, therapeutic use)
• Animals
• Cardiovascular Diseases (metabolism)
• Ceramides (metabolism, toxicity)
• Diabetes Mellitus, Type 2 (metabolism)
• Dioxanes (therapeutic use)
• Disease Models, Animal
• Fatty Acids (pharmacokinetics)
• Fatty Liver (metabolism)
• Gaucher Disease (drug therapy, genetics, metabolism)
• Glucosyltransferases (antagonists & inhibitors, physiology)
• Glycosphingolipids (metabolism)
• Humans
• Insulin Resistance (physiology)
• Metabolic Syndrome (metabolism)
• Mice
• Mice, Obese
• Non-alcoholic Fatty Liver Disease
• Obesity (metabolism)
• Pyrrolidines (therapeutic use)
• Receptor, Insulin (chemistry, physiology)
• Signal Transduction