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

Nir Barzilai, D. Massillon, L. Rossetti

Research output: Contribution to journalArticle

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Abstract

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
Volume310
Issue number3
StatePublished - 1995

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Metabolism
Rats
Fasting
Glucose-6-Phosphatase
Fats
Glucose-6-Phosphate
Glucose
Liver
Medical problems
Glycogen
Insulin
Clamping devices
Animals
Hyperinsulinism
Glycolysis
Insulin Resistance
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Effects of fasting on hepatic and peripheral glucose metabolism in conscious rats with near-total fat depletion. / Barzilai, Nir; Massillon, D.; Rossetti, L.

In: Biochemical Journal, Vol. 310, No. 3, 1995, p. 819-826.

Research output: Contribution to journalArticle

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abstract = "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.",
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