The impact of obesity, sex, and diet on hepatic glucose production in cats

Saskia Kley, Margarethe Hoenig, John Glushka, Eunsook S. Jin, Shawn C. Burgess, Mark Waldron, Erin T. Jordan, James H. Prestegard, Duncan C. Ferguson, Shaoxiong Wu, Darin E. Olson

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Obesity is a risk factor for type 2 diabetes in cats. The risk of developing diabetes is severalfold greater for male cats than for females, even after having been neutered early in life. The purpose of this study was to investigate the role of different metabolic pathways in the regulation of endogenous glucose production (EGP) during the fasted state considering these risk factors. A triple tracer protocol using 2H 2O, [U- 13C 3]propionate, and [3,4- 13C 2]glucose was applied in overnight-fasted cats (12 lean and 12 obese ; equal sex distribution) fed three different diets. Compared with lean cats, obese cats had higher insulin (P < 0.001) but similar blood glucose concentrations. EGP was lower in obese cats (P < 0.001) due to lower glycogenolysis and gluconeogenesis (GNG; P < 0.03). Insulin, body mass index, and girth correlated negatively with EGP (P < 0.003). Female obese cats had ∼1.5 times higher fluxes through phosphoenolpyruvate carboxykinase (P < 0.02) and citrate synthase (P < 0.05) than male obese cats. However, GNG was not higher because pyruvate cycling was increased 1.5-fold (P < 0.03). These results support the notion that fasted obese cats have lower hepatic EGP compared with lean cats and are still capable of maintaining fasting euglycemia, despite the well-documented existence of peripheral insulin resistance in obese cats. Our data further suggest that sex-related differences exist in the regulation of hepatic glucose metabolism in obese cats, suggesting that pyruvate cycling acts as a controlling mechanism to modulate EGP. Increased pyruvate cycling could therefore be an important factor in modulating the diabetes risk in female cats.

Original languageEnglish (US)
Pages (from-to)R936-R943
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4
StatePublished - Apr 2009


  • Diabetes mellitus
  • Nuclear magnetic resonance spectroscopy
  • Polyunsaturated fatty acids
  • Pyruvate cycling
  • Thyroxine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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