Sulfonylurea Stimulation of Insulin Secretion

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FIG. 3.
FIG. 3.

A: Whole-cell KATP currents recorded using a two-electrode voltage clamp from an intact oocyte expressing Kir6.2/SUR1, in response to a series of depolarizing and hyperpolarizing 10-mV pulses from a holding potential of −10 mV. Azide (3 mmol/l) and gliclazide (1 mmol/l) were added to the extracellular solution, as indicated. Methods are the same as those described in ref. 42. B: Mean relation between gliclazide concentration and inhibition of the Kir6.2/SUR1 current, measured in the intact oocyte (n = 6). The current evoked by a voltage step to −100 mV in the presence of gliclazide (I) is expressed as a fraction of its amplitude in the absence of the drug (IO). The solid line is the best fit of equation 1 to the data, with IC50 = 108 ± 3 nmol/l (n = 5), h = 0.81, and L = 0. The dotted line shows the fit obtained for gliclazide block of Kir6.2/SUR1 currents in the excised patch configuration (see Fig. 1). The dashed line shows the fit obtained for gliclazide block of the native β-cell KATP channel in whole-cell recordings from mouse pancreatic β-cells (IC50 = 184 nmol/l) (42). C: Relation between gliclazide concentration and inhibition of the Kir6.2/SUR1 current, measured in the inside-out patch in the presence of 100 μmol/l MgADP (n = 5). The current evoked by a voltage step to −100 mV in the presence of gliclazide (I) is expressed as a fraction of its mean amplitude in the absence of the drug (IO). The solid line is the best fit of equation 1 to the data, with IC50 = 204 nmol/l, h = 1.13, and L = 0.065. The dashed line shows the fit obtained in the absence of added nucleotide (adapted from Gribble et al. [19]).

This Article

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