Hepatic gluconeogenic capacity from various precursors in young versus old rats

Abstract

Hepatic gluconeogenic capacity was studied in young (4 months of age) and old (24 months of age) male Fischer 344 rats fasted for 24 hours using the isolated hepatocyte technique. Following the isolation of liver cells, the following precursors were added to the cell suspensions and incubated for 30 minutes: lactate (5 mmol/L), pyruvate (5 mmol/L), alanine (5 mmol/L), glutamine (5 mmol/L), oxaloacetate (5 mmol/L), glycerol (5 mmol/L), dihydroxyacetone (10 mmol/L), fructose (10 mmol/L), or saline (no precursor addition). To confirm that glucose production reflects gluconeogenic capacity, there was significant depletion of hepatic glycogen after the 24-hour fast and minimal alterations in glycogen content once substrates were added. Adjusting the gluconeogenic rates to reflect 100% cell viability resulted in no difference between young and old animals for any substrate used with the sole exception of fructose. The hepatic glucose production from fructose was 34% greater for young versus old animals. The results suggest that following a period of starvation the basal glucose production rates from hepatocytes, incubated with precursors entering the gluconeogenic pathway prior to fructose-6-phosphate, are equivalent in young and old rats.