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Model of insulin resistance in liver cells
Author(s) -
Nair Sandhya,
Stapleton Susan R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a293-e
Subject(s) - insulin resistance , insulin , insulin receptor , protein kinase b , phosphorylation , glycosylation , chemistry , biochemistry , insulin receptor substrate , glucosamine , medicine , biology , endocrinology
Insulin resistance, a hallmark of type 2 diabetes, is characterized by the inability of a cell or tissue to respond to physiological levels of insulin resulting in problems with glucose transport and metabolism. Several cellular models have been utilized to determine the mechanism of induction of insulin resistance but questions remain unanswered. There is evidence that high glucose induced insulin resistant may be mediated by products of the hexosamine biosynthetic pathway (HBP). The major end product of HBP, UDP‐GlcNAC, is the substrate for O‐GlcNAC transferase, an enzyme that catalyzes the O‐linked transfer of GlcNAC to Ser/Thr residues of numerous proteins. This modification may play a role in induction of insulin resistance and thus needs to be evaluated in different cell types to fully understand its implication. Therefore we developed an insulin resistant model in primary hepatocytes by treating the cells with a precursor of a HBP product, glucosamine, at various concentrations over differing lengths of time. Insulin resistance was considered established when signal proteins such as AKT and the MAPK family were no longer phosphorylated in the presence of insulin. Increased glycosylation of proteins was also observed. Treatment of these cells with selenium, an insulin‐mimetic, restored the phosphorylation of the signal proteins. Supported in part by a WMU FRACASF and Monroe Brown award and NSF DBI‐0139204.