Glucose and alanine metabolism during bacterial infections in rats and rhesus monkeys

To investigate the effects of bacterial infection on glucose and alanine metabolism, a variety of studies were carried out in rat and monkey models. These included glucose turnover by a pulse-dose technique in infected rats; alanine and glucose production and utilization in control and septic monkeys; in vivo measurement of gluconeogenesis in rats, with and without an alanine load; the in vitro rate of glucose formation from various substrates by isolated liver perfusion and hepatic cells; and in vivo rates of oxidation of glucose labeled with 14C at the 1 or 6 carbon position. In rats, glucose turnover was markedly accelerated 24 hr after inoculation of either 10(4) or 10(7) Streptococcus pneumoniae. Glucose utilization and production were also accelerated during illness and early recovery from a pneumococcal infection in monkeys. The rates of gluconeogenesis as measured by either a pulse technique in rats or continuous infusion of labeled alanine in monkey were significantly elevated during pneumococcal septicemia. During the agonal stages (10(7) of the pneumococcal infection in rat, an alanine load resulted in a decreased rate of labeled glucose production and an increase in plasma glucose when compared to values of fasted control rats. However, early illness caused similar or increased rates of glucose production from alanine in vivo. Similar reduced rates of glucose formation were observed when the isolated livers or hepatocytes from rats during the agonal stages of infection were perfused with excess quantities of gluconeogenic substrates. Thus, in the rat, gluconeogenic capacity (ability to form glucose from excess substrates) appears to decrease only during the agonal stages of pneumococcal infection. During acute pneumococcal sepsis in the rhesus monkey, alanine production and utilization were significantly elevated and it was estimated that over 90% of the newly produced alanine was utilized for glucose synthesis. When arterial--venous differences were measured across the hindquarters, significantly more alanine was released, presumably from skeletal muscle of the septic monkey, compared to the recovery period or in the control groups. Thus, the increase in glucose synthesis in both rat and monkey appears to be correlated with substrate availability and kinetic rate, rather than gluconeogenic capacity of the liver. The major increase in glucose utilization during both S. pneumoniae and Francisella tularensis live vaccine strain (LVS) infections in rat was a progressive elevation in the rate of oxidation via the pentose phosphate shunt in the rat. Further, the rate of oxidation appeared to be correlated with the magnitude of the bacteremia, which is an indication of the severity of the infection...