Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats

S. Renee Commerford, Jennifer B. Ferniza, Michael E. Bizeau, Jeffrey S. Thresher, Wayne T. Willis, Michael J. Pagliassotti

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


High-fat (HFD) and high-sucrose diets (HSD) reduce insulin suppression of glucose production in vivo, increase the capacity for gluconeogenesis in vitro, and increase glucose-6-phosphatase (G-6-Pase) activity in whole cell homogenates. The present study examined the effects of HSD and HFD on in vivo gluconeogenesis, the catalytic and glucose-6-phosphate translocase subunits of G-6-Pase, glucokinase (GK) translocation, and glucose cycling. Rats were fed a high-starch control diet (STD; 68% cornstarch), HSD (68% sucrose), or HFD (45% fat) for 7-13 days. The ratio of 3H in C6:C2 of glucose after 3H2O injection into 6- to 8-h-fasted rats was significantly increased in HSD (0.68 ± 0.07) and HFD (0.71 ± 0.08) vs. STD (0.40 ± 0.10). G-6-Pase activity was significantly higher in HSD and HFD vs. STD in both intact and disrupted liver microsomes. HSD and HFD significantly increased the amount of the p36 catalytic subunit protein, whereas the p46 glucose-6-phosphate translocase protein was increased in HSD only. Despite increased nonglycerol gluconeogenesis and increased G-6-Pase, basal glucose and insulin levels as well as glucose production were not significantly different among groups. Hepatocyte cell suspensions were used to ascertain whether diet-induced adaptations in glucose phosphorylation and GK might serve to compensate for upregulation of G-6-Pase. Tracer-estimated glucose phosphorylation and glucose cycling (glucose ↔ glucose 6-phosphate) were significantly higher in cells isolated from HSD only. After incubation with either 5 or 20 mM glucose and no insulin, GK activity (nmol·mg protein -1·min-1) in digitonin-treated eluates (translocated GK) was significantly higher in HSD (32 ± 4 and 146 ± 6) vs. HFD (4 ± 1 and 83 ± 10) and STD (9 ± 2 and 87 ± 9). Thus short-term, chronic exposure to HSD and HFD increase in vivo gluconeogenesis and the G-6-Pase catalytic subunit. Exposure to HSD diet also leads to adaptations in glucose phosphorylation and GK translocation.

Original languageEnglish (US)
Pages (from-to)E545-E555
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number3 46-3
StatePublished - Sep 1 2002
Externally publishedYes


  • Glucokinase
  • Glucose metabolism
  • Glucose-6-phosphatase
  • Liver

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


Dive into the research topics of 'Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats'. Together they form a unique fingerprint.

Cite this