Direct measurement of pulsatile insulin secretion from the portal vein in human subjects

Insulin is secreted in a high frequency pulsatile manner. These pulses are delivered directly into the portal vein and then undergo extraction and dil ution before delivery into the systemic circulation. The reported frequency of these insulin pulses estimated in peripheral blood varies from an inter pulse interval of 4-20 min. We postulated that this discrepancy is due to t he attenuation of the pulse signal in the systemic circulation vs. the port al circulation. In the present study we measured pulsatile insulin release directly in the portal circulation of human subjects who had indwelling tra nsjugular intrahepatic portasystemic stent shunts (TIPSS) to decompress por tal hypertension. We quantitated pulsatile insulin secretion in both the ov ernight fasted state (fasting) and during a hyperglycemic clamp (8 mmol/L). Direct portal vein sampling established that pulsatile insulin secretion i n humans has an interval (periodicity) of approximately 5 min. The amplitud e (and mass) of the insulin concentration oscillations observed in the port al vein was approximately 5-fold greater than that observed in the arterial ized vein and was similar to that observed in the dog. Increased insulin re lease during hyperglycemia was achieved through amplification of the insuli n pulse mass. In conclusion, direct portal vein sampling in humans revealed that the interpulse interval of insulin pulses in humans is about 5 min, a nd this frequency is also observed when sampling from the systemic circulat ion using a highly specific insulin assay and 1-min sampling, but is about 4-fold greater than the frequency observed at this site using single site R IAs. We confirm that enhanced insulin release in response to hyperglycemia is achieved by amplification of these high frequency pulses.