Response of phosphoenolpyruvate cycle activity to fasting and to hyperinsulinemia in human subjects. Wolfe, Robert R., David Chinkes, Hidefumi Baba, Judah Rosenblatt, and Xiao-Jun Zhang. Metabolism Unit, Shriners Burns Institute and University of Texas Medical Branch, 815 Market Street, Galveston, Texas 77550
APStracts 3:0044E, 1996.
We have used a new isotopic tracer technique to investigate the physiological role of the phosphoenolpyruvate (PEP) cycle in metabolic adaptation to fasting and to hyperinsulinemia. The forward direction of the PEP cycle is the conversion of oxaloacetate (OAA) to PEP, and the net flux of the cycle is the rate at which PEP from OAA goes on to form glucose or glycogen, as opposed to being recycled to pyruvate, then OAA. Normal volunteers (n = 6) were studied after an overnight fast and then again after three days of fasting, and five additional subjects were studied during a hyperinsulinemic clamp (insulin concentration = 568 +/- 25 _U/ml, glucose infusion = 14.2 +/- .55 mg/kg x min). After an overnight fast, 35.4 +/- 6.7% of PEP from OAA was recycled to pyruvate/lactate. Short-term fasting caused a significant increase in the conversion of OAA to PEP, and also a drop in the percent PEP from OAA that went to pyruvate/lactate to 15.2 +/- 4.0%. The principal response to hyperinsulinemia was a decrease in the recycling of OAA to lactate, as there was no significant change in the conversion of OAA to PEP. We conclude that changes in both directions of the PEP cycle are important in regulating gluconeogenic/glycogeneogenic flux.

Received 2 October 1995; accepted in final form 19 February 1996.
APS Manuscript Number E483-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96