Effects of gliquidone and glibenclamide on metabolic response and insulin receptor interaction in monocytes from patients with type 2 diabetes mellitus

In this double-mashed study, we compared the effects of 2 sulfonylureas-gli quidone (Gd) and glibenclamide (G1)-on metabolic control and on the interac tion of insulin with its receptor. After a 3-week run-in period, 43 untreat ed patients with type 2 diabetes mellitus, aged 47 to 60 years, were random ly allocated to receive treatment with Gd (n = 22) or G1 (n = 21) for 4 mon ths. Fasting plasma glucose levels decreased similarly in both treatment gr oups after 4 days and 4 months of treatment. After 4 months of treatment, a superimposable decrease in glycosylated hemoglobin Al, concentrations was seen compared with baseline values (Gd, 7.9 +/- 1.4% vs 6.5 +/- 0.6%; G1, 7 .6 +/- 1.5% vs 6.4 +/- 0.9%). No significant changes were noted between tre atment groups in body weight or in lipid or leptin levels. Total cell-assoc iated insulin (TCAI) to monocytes increased significantly in the Gd group a fter 4 days and after 4 months compared with baseline (baseline, 2.13 +/- 0 .9%; 4 days, 3.14 +/- 1.1%; 4 months, 4.33 +/- 0.8%; P < 0.01). The insulin internalization index also increased significantly (baseline, 0.60 +/- 0.2 ; 4 days, 0.80 +/- 0.1; 4 months, 0.90 +/- 0.1; P < 0.01). Finally, insulin degradation increased after 4 days (P < 0.01); however, no further improve ment was found after 4 months of therapy (baseline, 68.40 +/- 15.0%; 4 days , 84.30 +/- 8.0%; 4 months, 86.20 +/- 9.0%). In contrast, in the G1 group, after 4 days of treatment no significant changes were noted in TCAI, insuli n internalization index, or degradation. After long-term treatment, G1 sign ificantly increased TCAI (baseline, 2.30 +/- 0.8%; 4 months, 3.13 +/- 0.7%; P < 0.05) and the internalization index (baseline, 0.60 +/- 0.2%; 4 months , 0.73 +/- 0.1%; P < 0.05), but to a lesser degree than Gd. No effect of G1 on insulin degradation was detected. These data demonstrate that both drug s improve metabolic control in patients with type 2 diabetes mellitus. The difference in their effects on the insulin receptor might; be a consequence of the different kinetics of insulin secretion associated with their use. Moreover, only Gd ameliorated insulin degradation, suggesting a direct acti on of the drug on the degradative pathway of insulin and the existence of d ifferent actions of Gd and G1 on this process. Key words: gliquidone, glibe nclamide, metabolic control, insulin processing, insulin receptor.