The greater contribution of gluconeogenesis to glucose production in obesity is related to increased whole-body protein catabolism

Stéphanie Chevalier, Shawn C. Burgess, Craig R. Malloy, Réjeanne Gougeon, Errol B. Marliss, José A. Morais

Research output: Contribution to journalArticle

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Abstract

Obesity is associated with an increase in the fractional contribution of gluconeogenesis (GNG) to glucose production. We tested if this was related to the altered protein metabolism in obesity. GNGPEP (via phosphoenol pyruvate [PEP]) was measured after a 17-h fast using the deuterated water method and 2H nuclear magnetic resonance spectroscopy of plasma glucose. Whole-body 13C-leucine and 3Hglucose kinetics were measured in the postabsorptive state and during a hyperinsulinemic-euglycemic- isoaminoacidemic clamp in 19 (10 men and 9 women) lean and 16 (7 men and 9 women) obese nondiabetic subjects. Endogenous glucose production was not different between groups. Postabsorptive %GNGPEP and GNG PEP flux were higher in obese subjects, and glycogenolysis contributed less to glucose production than in lean subjects. GNGPEP flux correlated with all indexes of adiposity and with postabsorptive leucine rate of appearance (Ra) (protein catabolism). GNGPEP was negatively related to the clamp glucose rate of disposal (Rd) and to the protein anabolic response to hyperinsulinemia. In conclusion, the increased contribution of GNG to glucose production in obesity is linked to increased postabsorptive protein catabolism and insulin resistance of both glucose and protein metabolism. Due to increased protein turnover rates, greater supply of gluconeogenic amino acids to the liver may trigger their preferential use over glycogen for glucose production.

Original languageEnglish (US)
Pages (from-to)675-681
Number of pages7
JournalDiabetes
Volume55
Issue number3
StatePublished - Mar 2006

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Gluconeogenesis
Obesity
Glucose
Proteins
Glucose Clamp Technique
Pyruvic Acid
Leucine
Glycogenolysis
Adiposity
Hyperinsulinism
Glycogen
Insulin Resistance
Magnetic Resonance Spectroscopy
Amino Acids
Water
Liver

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

The greater contribution of gluconeogenesis to glucose production in obesity is related to increased whole-body protein catabolism. / Chevalier, Stéphanie; Burgess, Shawn C.; Malloy, Craig R.; Gougeon, Réjeanne; Marliss, Errol B.; Morais, José A.

In: Diabetes, Vol. 55, No. 3, 03.2006, p. 675-681.

Research output: Contribution to journalArticle

Chevalier, Stéphanie ; Burgess, Shawn C. ; Malloy, Craig R. ; Gougeon, Réjeanne ; Marliss, Errol B. ; Morais, José A. / The greater contribution of gluconeogenesis to glucose production in obesity is related to increased whole-body protein catabolism. In: Diabetes. 2006 ; Vol. 55, No. 3. pp. 675-681.
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