THE EFFECT OF GLUCOSE-CONCENTRATION ON INSULIN-INDUCED 3T3-L1 ADIPOSECELL-DIFFERENTIATION

We examined the effect of glucose concentration on insulin-induced 3T3 -L1 adipose cell differentiation. Oil Red O staining of neutral lipid, cellular triglyceride mass, and glycerol phosphate dehydrogenase (GPD H) activity, were greater in 3T3-L1 cells cultured at 5 mM vs. 25 mM g lucose. GPDH activity was 2- to ii-fold higher at 5 mM vs. 25 mM gluco se over a range of insulin concentrations (0.1 to 100 nM). Insulin-sti mulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS- 1) was 1.7-fold greater, and insulin-stimulated phosphoinositide 3-kin ase association with IRS-1 was 2.3-fold higher, at 5 mM vs. 25 mM gluc ose. These effects of glucose were not caused by alterations in IRS-1 mass or cell-surface insulin binding. In preadipose cells at 5 mM gluc ose, expression of the leukocyte antigen-related (LAR) protein tyrosin e phosphatase (negative regulator of insulin signaling) was 63% of the level at 25 mM glucose. Our data demonstrate that glucose concentrati on affects insulin-induced 3T3-L1 adipose cell differentiation as well as differentiation-directed insulin signaling pathways. Alterations i n LAR expression potentially may be involved in modulating these respo nses.