Effect of nicotinamide on carbohydrate metabolism in the rat liver during starvation.

Abstract

Abstract. A single high dose of nicotinamide (500 mg/kg body weight) results in an eight‐hour long inhibition of lipolysis in adipose tissue by transformation to nicotinic acid. In the present paper the effect of inhibited lipolysis on carbohydrate and amino acid metabolism after forty‐eight hours starvation was examined in vivo. Within two hours after the injection of nicotinamide (Nam) the plasma level of FFA declines from 900 μval/l to 300 μval/l. The FFA level rises again between 8–12 h after Nam injection. The reduced supply of FFA to the liver leads to a reduced oxidation rate, characterized by a fall in the acetyl‐CoA content of the liver and of ketone bodies in liver and blood. Simultaneously there is an increase in protein catabolism. This increase is characterized by increased urinary excretion of urea up to 10 h after Nam injection and by a higher urea production rate in liver slices of rats pretreated with Nam. In the liver the levels of the following amino acids rise very sharply SER (100%), CIT (400%), ORN (250%), ALA (300%), α‐AB (470%), VAL (350%), LEU (250%), ILE (370%). The content of THR is reduced to 63%, and GLY to 50%. In comparison to the values of the control groups the contents of ASP, GLU, TYR, LYS, HIS and ARG are unchanged.The result of the increased precursor supply for gluconeogenesis is a higher rate of glucose production, characterized by an increase in blood glucose by 40 mg/100 ml, by an increase in liver glycogen content, by an increase in the concentrations of intermediates of the Embden‐Meyerhof‐pathway (mainly the concentrations of PEP (870%), 3PGA (480%), FDP (150%), G6P (250%) and glucose (220%). In liver slice experiments the glucose production rate from L‐ALA rises significantly, compared to the control group, after pretreatment of the animals with Nam. The results show that a stimulation of gluconeogenesis is obtainable in vivo, although the oxidation rate of FFA is reduced. Thus, they support the assumption, that an increased fatty acid oxidation rate is not a primary condition of stimulated gluconeogenesis.