AJP - Endocrinology and Metabolism, Vol 261, Issue 4 E473-E478, Copyright © 1991 by American Physiological Society
Basal and insulin-mediated carbohydrate metabolism in human muscle deficient in phosphofructokinase 1
A. Katz, M. K. Spencer, S. Lillioja, Z. Yan, D. M. Mott, R. G. Haller and S. F. Lewis
Department of Kinesiology, University of Illinois, Urbana 61801.
Biopsies were obtained from the quadriceps femoris muscle of two male
patients deficient in phosphofructokinase (PFK) 1. In the basal state the
patients had markedly higher contents of UDP-glucose (approximately
5-fold), hexose monophosphates (approximately 7- to 13-fold), inosine
monophosphate (IMP) (approximately 15-fold), and fructose 2,6-bisphosphate
(F-2,6-P2; approximately 6-fold) than controls. Fructose 1,6-bisphosphate
was not detectable, and phosphocreatine was lower (33 and 54 mmol/kg dry
wt) than in controls [72 +/- 4 (SD)]. Patients had normal fasting plasma
glucose and insulin levels and basal glucose turnover rates and responded
normally to a 75-g oral glucose challenge. Patients were also studied
during euglycemic hyperinsulinemia (approximately 95 mg/dl; 40 and 400
mU.m-2.min-1). Whole body glucose disposal rates were normal during both
insulin infusion rates. Biopsies taken after the 400 mU insulin infusion
showed decreases in acetylcarnitine and citrate and increases in the
fractional activity of glycogen synthase. It is suggested that the high
basal levels of F-2,6-P2 are, at least partly, a consequence of the high
levels of fructose 6-phosphate, which will stimulate flux through PFK-2 and
inhibit fructose-2,6-bisphosphatase. The low phosphocreatine and high IMP
contents indicate that carbohydrate availability is important for control
of high-energy phosphate metabolism, even in the basal state. The
insulin-mediated decreases in acetylcarnitine and citrate suggest an
activation of the tricarboxylic acid cycle in skeletal muscle but an
absence of the normal response to replenish these intermediates.
