Insulin-dependent diabetes mellitus in mice does not alter liver heparan sulfate.
Diabetes -associated hyperlipidemia is generally attributed to reduced clearance of plasma lipoproteins, especially remnant lipoproteins enriched in cholesterol and triglycerides. Hepatic clearance of remnants occurs via low density lipoprotein receptors and the heparan sulfate proteoglycan, syndecan-1. Previous studies have suggested alterations in heparan sulfate proteoglycan metabolism in rat and mouse diabetic models, consistent with the idea that diabetic dyslipidemia might be caused by alterations in proteoglycan expression in the liver. In this study we analyzed the content and composition of liver heparan sulfate in streptozotocin-induced insulin-deficient diabetic mice that displayed fasting hypertriglyceridemia and delayed clearance of dietary triglyceride-rich lipoproteins. No differences between normal and diabetic littermates in liver heparan sulfate content, sulfation, syndecan-1 protein levels, or affinity for heparin-binding ligands, such as apolipoprotein E or fibroblast growth factor-2, were noted. Decreased incorporation of [(35)S]sulfate in insulin-deficient mice in vivo was observed, but the decrease was due to increased plasma inorganic sulfate, which reduced the efficiency of labeling of liver heparan sulfate. These results show that hyperlipidemia in insulin-deficient mice is not due to changes in hepatic heparan sulfate composition.
Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093, USA.
Joseph R
JR
Bishop
Erin
E
Foley
Roger
R
Lawrence
Jeffrey D
JD
Esko
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001057:Apolipoproteins E / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000209:etiology / Q000473:pathology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013311:Streptozocin / Q000633:toxicity; D015238:Sulfotransferases / Q000502:physiology; D053668:Syndecan-1 / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D001057:Apolipoproteins E; D001786:Blood Glucose; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D013311:Streptozocin; D015238:Sulfotransferases; D053668:Syndecan-1; C021350:heparitin sulfotransferase