Glycomics investigation into insulin action.
Defects in glycosylation are becoming increasingly associated with a range of human diseases. In some cases, the disease is caused by the glycosylation defect, whereas in others, the aberrant glycosylation may be a consequence of the disease. The implementation of highly sensitive and rapid mass spectrometric screening strategies for profiling the glycans present in model biological systems is revealing valuable insights into disease phenotypes. In addition, glycan screening is proving useful in the analysis of knock-out mice where it is possible to assess the role of glycosyltransferases and glycosidases and what function they have at the cellular and whole organism level. In this study, we analysed the effect of insulin on the glycosylation of 3T3-L1 cells and the effect of insulin resistance on glycosylation in a mouse model. Transcription profiling of 3T3-L1 cells treated with and without insulin revealed expression changes of several glycogenes. In contrast, mass spectrometric screening analysis of the glycans from these cells revealed very similar profiles suggesting that any changes in glycosylation were most likely on specific proteins rather than a global phenomenon. A fat-fed versus carbohydrate-fed mouse insulin resistant model was analysed to test the consequences of chronic insulin resistance. Muscle and liver N-glycosylation profiles from these mice are reported.
Division of Molecular Biosciences, Imperial College, London, South Kensington, UK.
Simon
S
Parry
Dirk
D
Hadaschik
Christine
C
Blancher
Mande K
MK
Kumaran
Natalia
N
Bochkina
Howard R
HR
Morris
Sylvia
S
Richardson
Timothy J
TJ
Aitman
Dominique
D
Gauguier
Ken
K
Siddle
James
J
Scott
Anne
A
Dell
D041721:3T3-L1 Cells; D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000032:analysis*; D006031:Glycosylation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009132:Muscles / Q000737:chemistry; D011134:Polysaccharides / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic / Q000187:drug effects
D006023:Glycoproteins; D007328:Insulin; D011134:Polysaccharides