Glycosphingolipids and insulin resistance

Mirjam Langeveld, Johannes M. F. G. Aerts

Research output: Contribution to journalReview articleAcademicpeer-review

91 Citations (Scopus)

Abstract

Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple sphingolipid, directly inhibits phosphorylation of the insulin signaling mediator Akt/Protein Kinase B. More complex glycosphingolipids, so-called gangliosides, block phosphorylation of the insulin receptor and down-stream signaling, possibly by exclusion of the insulin receptor from specific membrane domains. Pharmacological inhibition of glycosphingolipid synthesis is found to markedly improve insulin sensitivity in rodent models of insulin resistance. Partial glycosphingolipid reduction is well tolerated and may thus offer an attractive new treatment modality for obesity-induced insulin resistance and type II diabetes
Original languageEnglish
Pages (from-to)196-205
JournalProgress in lipid research
Volume48
Issue number3-4
DOIs
Publication statusPublished - 2009

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