REGULATION OF GLUCOSE TRANSPORTERS AND HEXOSE UPTAKE IN 3T3-L1 ADIPOCYTES - GLUCAGON-LIKE PEPTIDE-1 AND INSULIN INTERACTIONS

Glucagon-like peptide-1 (7-36 amide) (GLP-1) is known to increase insu lin release when given as a bolus in the fasted and fed state. GLP-1 a lso increases glucose uptake and lipid synthesis in cultured adipocyte s. In this study we investigated the effects of GLP-1 on glucose uptak e and on the levels of expression of the facilitative glucose transpor ters, GLUT1 and GLUT4, in fully differentiated 3T3-L1 adipocytes. Cell s were incubated with GLP-1 (10 nM) with or without insulin (10 and 10 0 nM) for 24 h. Under these conditions, GLP-1 alone caused an increase in basal and acute insulin-stimulated glucose uptake along with an in crease in GLUT1 and GLUT4 protein levels. However, there was no change in the expression of GLUT1 and GLUT4 mRNAs. In the absence of GLP-1, prolonged exposure to insulin caused a marked reduction in the levels of GLUT4 mRNA and protein, and an inhibition of glucose uptake after a n acute exposure to insulin. This insulin-induced down-regulation of G LUT4 was prevented when GLP-1 was present during the 24-h treatment. I n contrast, the acute insulin-stimulated glucose uptake could not be r estored by GLP-1. GLP-1 is therefore the first gut hormone shown to be capable of modulating glucose transporter levels in cultured adipocyt es.