Effects of fasting on hepatic and peripheral glucose metabolism in conscious rats with near-total fat depletion

N. Barzilai, D. Massillon, L. Rossetti

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Experimental diabetes and fasting are both associated with hypoinsulinaemia and share several other metabolic features. We investigated hepatic and peripheral glucose metabolism in young rats after near-total depletion of their fat mass. Conscious rats were fasted for 72 h (n = 13), while 6 h-fasted animals (n = 14) served as controls. Rats were studied either during saline infusion or insulin (18 m-units/kg per min)-clamp studies. In fasting, despite a 2-fold increase in hepatic glucose-6-phosphatase (Glc-6-Pase) V(max.) (from 16 ± 2 μmol/g of liver per min in control; P < 0.001), the basal hepatic glucose production (HGP) decreased by 47% [from 88 ± 3 μmol/kg lean body mass (LBM) per min in control; P < 0.01]. The decreased HGP in fasting was associated with a 70% decrease in the hepatic levels of glucose 6-phosphate (Glc-6-P) (from 366 ± 53 nmol/g wet wt. in control; P < 0.01). Thus Glc-6-Pase activity assayed in the presence of the Glc-6-P levels found in vivo was decreased by 44%. During hyperinsulinaemia, peripheral glucose uptake was decreased by 15% with 3 days of fasting (from 272 ± 17 μmol/kg LBM per min in control; P < 0.01). This was completely accounted for by a 42% decrease in whole-body glycolysis (P < 0.01), while the rate of glycogen synthesis was unchanged. Thus fasting (after near-total fat depletion) differs from experimental diabetes because: (1) despite markedly increased Glc-6-Pase, HGP is decreased in fasting, due to a marked decrease in the substrate level (Glc-6-P) in vivo; and (2) the impairment in peripheral insulin sensitivity in fasting is due to a decrease in the glycolytic, and not the glycogen-synthetic, pathway.

Original languageEnglish (US)
Pages (from-to)819-826
Number of pages8
JournalBiochemical Journal
Issue number3
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Effects of fasting on hepatic and peripheral glucose metabolism in conscious rats with near-total fat depletion'. Together they form a unique fingerprint.

Cite this