Monocyte membrane lipid composition, fluidity, and insulin binding were studied in 10 previously untreated obese type II (non-insulin-dependent) diabetic subjects before and 2-7 days, 1 mo, and 3 mo after glyburide therapy. A significant reduction in fasting blood glucose levels occurred within 1 wk after initiation of therapy in all subjects. Serum insulin levels did not change significantly. After a transient increase at 2-7 days, insulin binding and receptor number decreased to less than pretreatment levels after 3 mo of therapy despite continued improved glycemic control. Molar cholesterol-phospholipid ratios increased significantly at 2-7 days and then reverted to pretreatment levels. A significant positive correlation between insulin binding and cholesterol-phospholipid ratios was seen at all durations of treatment. Membrane microviscosity as measured by fluorescence polarization of the probe diphenylhexatriene was significantly decreased after 3 mo of therapy. The results indicate that the glycemic effect of glyburide represents enhancement of insulin action and occurs independently of membrane insulin receptors.

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