Two types of studies have been done to determine the importance of the rate of plasma glucose concentration change to the magnitude of the acute insulin response following an intravenous glucose injection in normal men. When an identical amount of glucose (20 g) was given at varying infusion rates (1.67 g/min to 66.7 g/min), the magnitude of the acute insulin response was found to be proportional to the rate. When various doses (5 g to 20 g) were given at the identical rate (1.67 g/min) the acute insulin response did not change. When 5 g of glucose was given in 0.3 and 3 minutes, a sub-maximal acute insulin response resulted which was still rate-dependent (delta peak IRI=35.5 +/- 5 at 5 g/0.3 minutes, 21.8 +/- 3 at 5 g/3 minutes). We have concluded that the human islet acts as a sensor for both the concentration of plasma glucose and the rate of change in plasma glucose. Islet perception of both these phenomena are critical factors in the determination of the magnitude of the acute insulin response.