THE EFFECT OF GLYBURIDE ON BETA-CELL SENSITIVITY TO GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE

OBJECTIVE - To assess whether treatment with glyburide alters beta-cell sensitivity to GIP in NIDDM patients. RESEARCH DESIGN AND METHODS - We studied 5 untreated NIDDM patients in a meal study (Ensure, 240 ml/M2) and a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above fasting). From 60 to 120 min of the damp, GIP was infused in a primed continuous manner at a rate of 2 pmol . kg-1 . min-1. Subjects then were treated with glyburide. After they had been on a stable dose of medication for 1 mo, the meal study and glucose clamp studies were repeated. RESULTS - In response to treatment, a decrease in fasting glucose and an increase in weight was observed (1 2.8 +/- 1.8 vs. 8.5 +/- 0. 8 mM and 74.3 +/- 6.3 vs. 76.1 +/- 6.3 kg, respectively, P < 0.05). In response to the meal study, the AUC for glucose was less, for insulin was increased, and for GIP was unchanged after treatment (16.9 +/- 2.1 vs. 12.6 +/- 6.9 mM, P <0.05; 161 +/- 47 vs. 242 +/- 60 pM, P <0.05; and 199 +/- 22 vs. 219 +/- 18 pM, respectively). During the hyperglycemic clamp, steady-state glucose and 90- to 120-min GIP values were equivalent before and after treatment (18.0 +/- 1.3 vs. 18.3 +/- 1.3 mM and 302 +/- 59 vs. 298 +/- 37 pM, respectively). The 90-120 min insulin responses to the hyperglycemic clamp were greater after therapy (123 +/- 37 vs. 283 +/- 80 pM, P < 0.05) reflecting increased beta-cell responses to GIP. CONCLUSIONS - We conclude that glyburide enhances beta-cell sensitivity to GIP.