Glucose tolerance and insulin release in l-asparaginase treated rabbits

Abstract

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 an 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 produces a hyperinsulinemic diabetes in New Zealand White Rabbits that appears to persist in a mild form for at least 9–15 wk.