Objective— To assess whether treatment with glyburide alters β-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 clamp, 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 (12.8 ± 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 90b–120 min insulin responses to the hyperglycemic clamp were greater after therapy (123 ± 37 vs. 283 ± 80 pM, P < 0.05) reflecting increased β-cell responses to GIP.
Conclusions— We conclude that glyburide enhances β-cell sensitivity to GIP.
