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, S. F. Lewis

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 (~5-fold), hexose monophosphates (~7- to 13-fold), inosine monophosphate (IMP) (~15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; ~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 (~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- 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume261
Issue number4 24-4
StatePublished - 1991

Fingerprint

Phosphofructokinase-1
Carbohydrate Metabolism
Muscle
Acetylcarnitine
Insulin
Glucose
Muscles
Inosine Monophosphate
Phosphocreatine
Biopsy
Quadriceps Muscle
Citric Acid
Phosphofructokinase-2
Uridine Diphosphate Glucose
Phosphofructokinases
Glycogen Synthase
Hexoses
Citric Acid Cycle
Hyperinsulinism
Metabolism

Keywords

  • euglycemic hyperinsulinemia
  • fructose 2,6-bisphosphate
  • glucose 1,6-bisphosphate
  • glycogen
  • glycogen phosphorylase
  • glycogen synthase
  • glycogen synthase phosphatase
  • hexose monophosphates
  • high-energy phosphates
  • tricarboxylic acid cycle intermediates

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

Basal and insulin-mediated carbohydrate metabolism in human muscle deficient in phosphofructokinase 1. / Katz, A.; Spencer, M. K.; Lillioja, S.; Yan, Z.; Mott, D. M.; Haller, R. G.; Lewis, S. F.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 261, No. 4 24-4, 1991.

Research output: Contribution to journalArticle

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abstract = "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 (~5-fold), hexose monophosphates (~7- to 13-fold), inosine monophosphate (IMP) (~15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; ~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 (~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- 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.",
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T1 - Basal and insulin-mediated carbohydrate metabolism in human muscle deficient in phosphofructokinase 1

AU - Katz, A.

AU - Spencer, M. K.

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AU - Yan, Z.

AU - Mott, D. M.

AU - Haller, R. G.

AU - Lewis, S. F.

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N2 - 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 (~5-fold), hexose monophosphates (~7- to 13-fold), inosine monophosphate (IMP) (~15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; ~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 (~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- 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.

AB - 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 (~5-fold), hexose monophosphates (~7- to 13-fold), inosine monophosphate (IMP) (~15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; ~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 (~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- 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.

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KW - glycogen synthase phosphatase

KW - hexose monophosphates

KW - high-energy phosphates

KW - tricarboxylic acid cycle intermediates

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