title: 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: Department of Medical Biochemistry, University of Amsterdam, The Netherlands. j.m.aerts@amc.uva.nl
authors: Johannes M
authors: JM
authors: Aerts
authors: Rolf G
authors: RG
authors: Boot
authors: Marco
authors: M
authors: van Eijk
authors: Johanna
authors: J
authors: Groener
authors: Nora
authors: N
authors: Bijl
authors: Elisa
authors: E
authors: Lombardo
authors: Florence M
authors: FM
authors: Bietrix
authors: Nick
authors: N
authors: Dekker
authors: Albert K
authors: AK
authors: Groen
authors: Roelof
authors: R
authors: Ottenhoff
authors: Cindy
authors: C
authors: van Roomen
authors: Jan
authors: J
authors: Aten
authors: Mireille
authors: M
authors: Serlie
authors: Mirjam
authors: M
authors: Langeveld
authors: Tom
authors: T
authors: Wennekes
authors: Hermen S
authors: HS
authors: Overkleeft
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism / Q000633:toxicity; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004146:Dioxanes / Q000627:therapeutic use; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000493:pharmacokinetics; D005234:Fatty Liver / Q000378:metabolism; D005776:Gaucher Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors / Q000502:physiology; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D024821:Metabolic Syndrome / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use; D011972:Receptor, Insulin / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction
chemical_list: C520404:(2-(2',3'-dihydrobenzo(1,4)dioxin-6'-yl)-2-hydroxy-1-pyrrolidin-1-ylmethylethyl)nonanoic acid amide; D002518:Ceramides; D004146:Dioxanes; D005227:Fatty Acids; D006028:Glycosphingolipids; C496281:N-(5-adamantane-1-yl-methoxy-pentyl)deoxynojirimycin; D011759:Pyrrolidines; D017485:1-Deoxynojirimycin; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; D011972:Receptor, Insulin; D000218:Adamantane