TY - JOUR
T1 - Glycosphingolipids and insulin resistance
AU - Langeveld, Mirjam
AU - Aerts, Johannes M. F. G.
PY - 2009
Y1 - 2009
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.plipres.2009.03.002
DO - https://doi.org/10.1016/j.plipres.2009.03.002
M3 - Review article
C2 - 19303901
SN - 0163-7827
VL - 48
SP - 196
EP - 205
JO - Progress in lipid research
JF - Progress in lipid research
IS - 3-4
ER -