Sulfonylurea Stimulation of Insulin Secretion

TABLE 1

Comparison of the IC50 for KATP channel inhibition by various sulfonylureas with the Kd for drug binding

SUR1
SUR2A
SUR2B
IC50 (current) Kd (binding) IC50 (current) Kd (binding) IC50 (current) Kd (binding)
Glibenclamide (nmol/l) 0.13 [22] ≈0.7 *,[22] 45 [22] ≈300 (*,)[22] 42 [22] ≈350 *,(,)[22]
4.2 [21] 7.1 *[32] 27 [21] 1,200 *,[14] 43 [23] 6.3 , 32 *[23]
1.5 , 1.8*[41] 166 [36]
0.2 {}[55]
Glipizide (nmol/l) 3.8 [22] ≈17 *,[22] ≈6,000 (*,)[22] 1,200 [22] ≈6,000 *,(,)[22]
Glimepiride (nmol/l) 3.0 [34] 5.4 [34] 7.3 [34]
Tolbutamide (μmol/l) 4.9 [22] ≈29 *,[22] 85 [22] ≈270 (*,)[22] 88 [22] ≈280 *,(,)[22]
5.4 [21] 140 *[32] ≥ nmol/l [21,54]
10.5 [52] 9 {}[55] >1 mmol/l [55]
Gliclazide (nmol/l) 50 [21] >100 μmol/l [21]
Meglitinide (μmol/l) 1.2 [22] ≈7 *[22] 0.53 [21] ≈7 (*)[22] 1.6 [22] ≈8 (*)[22]
0.26 [21]
Mitiglinide (nmol/l) ≈60 [32] 280 *[32] > 100 μmol/l [32] >100 μmol/l [32]
3.8 [33] 3200 [33] 4,600 [33]
Repaglinide (nmol/l) 5.6 [53] 1,600 *[32] 2.2 [53] 2.0 [53]
21 [55] 0.6 {}[55]
Nateglinide (μmol/l) 8 *[32]
0.8 [55] 0.2 {}[55]
  • Only studies on recombinant SUR (indicated) are listed.

  • *

    * SURx expressed in the absence of Kir6.2;

  • SURx coexpressed with Kir6.2;

  • SURx coexpressed with Kir6.1. The Kd was measured by displacement of [3H] glibenclamide or, if no data were available, of [3H]P1075 (indicated by round brackets) or iodo-glibenclamide (

  • ) or [3H]repaglinide (indicated by curly brackets). Numbers in square brackets indicate references.

This Article

  1. Diabetes vol. 51 no. suppl 3 S368-S376