The physiological action of gliclazide: beta-cell function and insulin resistance

There is continuing debate about the physiological mechanisms of the action of sulphonylureas in man. In those patients taking sulphonylureas insulin secretion can be demonstrated to be higher, but there are also data which have been interpreted as evidence that these drugs may cause an alteration in peripheral insulin sensitivity. The physiological effects of the sulphonylurea gliclazide in diabetic subjects has been examined using a variety of experimental protocols to address this question: an intravenous gliclazide infusion, experiments using glucose clamping, mathematical modelling of the insulin and glucose data from subjects on and off gliclazide therapy, and the infusion of amino acids and glucose separately or in combination. The data from all these analyses suggest that the primary effect of gliclazide is on the beta-cell and that any effects on the peripheral insulin sensitivity are either slight or secondary to the improvement of the secretory capacity of the pancreatic islets.