1. Sulphonylurea derivatives are commonly used in the treatment of non-insulin-dependent diabetes mellitus. It is, however, unclear whether the hypoglycaemic effect of sulphonylurea derivatives is additive to the effect of glucose, or whether sulphonylurea derivatives act by increasing B-cell glucose sensitivity.

2. We assessed the effect of gliclazide on glucose-stimulated insulin secretion in eight healthy volunteers. Sixty minute hyperglycaemic glucose clamps (blood glucose levels of 8, 11 and 32 mmol/l) were performed, with and without prior administration of gliclazide (80 mg) 90 min before the glucose clamp.

3. Dose-response characteristics were assessed with a modified Michaelis-Menten equation. The Vmax. (maximal B-cell responsiveness) was not significantly changed (1.5 ± 0.1 versus 1.3 ± 0.2 and 5.0 ± 0.5 versus 4.8 ± 0.5 mmol/l for the first- and second-phase insulin secretion, respectively), whereas the ED50 (half-maximally stimulating blood glucose concentration) was significantly decreased by gliclazide for first-phase insulin secretion (7.6 ± 0.3 versus 9.1 ± 0.6 mmol/l) but not for second-phase insulin secretion (12.0 ± 0.5 versus 12.3 ± 0.5 mmol/l).

4. We conclude that gliclazide indeed leads to a shift to the left of the dose-response curve of first-phase insulin release in vivo without a change in Vmax., which indicates an apparent enhancement of B-cell glucose sensitivity.

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