ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN

ABSTRACT The initial as well as the late plasma insulin responses to low and high dose glucose infusions were enhanced by iv administration of tolbutamide in eight normal subjects. When expressed as change of the dose-response relationship between blood glucose level and plasma insulin response, the effect of tolbutamide consisted of a shift to the left of the dose-response curve, without increasing the maximum insulin response. This indicates that the drug acts as a sensitizer of the pancreas to the insulinogenic effect of glucose. In this respect, the effect of tolbutamide was of a similar nature both with regard to the initial and late insulin responses. The administration of tolbutamide at the beginning or towards the end of the one hour glucose infusion resulted in comparable enhancements of the late insulin response. Therefore, the effect of tolbutamide on the pancreas seems to be instantaneous, and does not change with prolonged exposure to the drug. Adrenaline, in a moderate dose, inhibited the synergism between glucose and tolbutamide. Since adrenaline in this dose probably does not interfere with glucose metabolism in the β-cell, it is concluded that tolbutamide does not act by modifying the metabolism of glucose, but rather by enhancing its direct insulinogenic signal in the β-cell.