Glucose tolerance an insulin release in L-asparaginase treated rabbits

Male New Zealand White Rabbits were injected intravenously with either a single dose of 10,000 IU Escherichia coli L-asparaginase/kg body weight containing 80 mg of D-mannitol/10,000 IU E. coli L-asparaginase or 80 mg D-mannitol kg/body weight alone. Elevated fasting glucose (G) and elevated fasting immunoreactive insulin (IRI) levels were observed in the L-asparaginase treated rabbits at 1 wk. They peaked at 3 wk and declined thereafter. However, fasting G and IRI levels remained significantly elevated at the end of the study (9-15 wk after injection) compared to preinjection levels and levels of the controls. Glucose and IRI levels 0.5 hr post and intravenous glucose load (1 g/kg body weight) also became elevated post L-asparaginase and followed a time course similar to that of the fasting G and IRI levels. These 0.5-hr levels also remained significantly elevated at the end of the study. These data show that a single dose of 10,000 IU/kg body weight produced a hyperinsulinemic diabetes in New Zealand White Rabbits that appears to persist in a mild form for at least 9-15 week.