Paradoxically enhanced glucose production during exercise in humans with blocked glycolysis caused by muscle phosphofructokinase deficiency

John Vissing, Henrik Galbo, Ronald G. Haller

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Muscle phosphofructokinase deficiency (PFKD) is characterized by exercise intolerance due to the enzymatic block in muscle glycolysis. Glucose infusion increases exertional fatigue in these patients, probably by decreasing the availability of free fatty acids (FFA) and ketones, which play a crucial role in ATP production during exercise in PFKD. This suggests that a lower than normal hepatic glucose production would be appropriate during exercise in PFKD. To investigate glucoregulation in PFKD, we measured glucose turnover and hormonal and metabolic responses to 20 minutes of cycle exercise at near maximal effort in three patients with PFKD and in healthy matched controls studied at the same absolute (A, 15 to 30 Watts) and relative (R, 35 to 80 Watts, matched heart rates) work load as the patients. During exercise, mean glucose production was higher in all patients versus controls (30 ± 4 versus A: 18 ± 2 and R: 20 ± 1 μmol · min-1 · kg-1). Mean glucose utilization during exercise was similar in patients and controls working at the same relative work load and higher than in controls at the low work load. Exercise-induced increases in arterialized blood were higher in all patients for glucose, FFA, growth hormone, glucagon, and norepinephrine. Plasma alanine and lactate always decreased during exercise in patients and consistently increased in controls. In conclusion, an enhanced neuroendocrine response and a paradoxically exaggerated mobilization of glucose occurs during exercise in PFKD. The responses are probably initiated by neural feedback elicited by disturbances in local muscle metabolism. The responses promote delivery of oxidizable fat to muscle, but at the expense of accumulation and futile cycling of glucose.

Original languageEnglish (US)
Pages (from-to)766-771
Number of pages6
JournalNeurology
Volume47
Issue number3
StatePublished - Sep 1996

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Glycogen Storage Disease Type VII
Glycolysis
Phosphofructokinases
Exercise
Glucose
Workload
Nonesterified Fatty Acids
Muscles
Substrate Cycling
Ketones
Glucagon
Alanine
Growth Hormone
Fatigue
Lactic Acid
Norepinephrine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Paradoxically enhanced glucose production during exercise in humans with blocked glycolysis caused by muscle phosphofructokinase deficiency. / Vissing, John; Galbo, Henrik; Haller, Ronald G.

In: Neurology, Vol. 47, No. 3, 09.1996, p. 766-771.

Research output: Contribution to journalArticle

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