Effect of theophylline on glucagon and glucose-mediated plasma insulin responses in subhuman primate fetus and neonate.

Abstract

The fetal and maternal plasma glucose and insulin, and the fetal growth hormone responses to the fetal administration of theophylline combined with either glucagon or glucose were examined in the subhuman primate fetus (Macaca mulatta) in late gestation. Theophylline enhanced and potentiated the fetal insulin responses to glucagon. Glucose combined with theophylline elicited a prompt rise in fetal plasma insulin, whereas glucose or theophylline alone did not. The neonate responded similarly to the combined theophylline and glucose injections with a prompt increase in plasma insulin levels. Fetal and neonatal plasma insulin levels were also promptly increased during the infusion of the dibutyryl derivative of cyclic 3′,5′ adenosine monophosphate to the fetus and neonate, respectively. Growth hormone levels were not altered in a consistent pattern during any of these experiments. These data indicate that the defect in the fetal and neonatal pancreatic betacell response to glucose is in the insulin releasing mechanism, rather than the synthesis of the hormone. Whether the apparent insensitivity of the fetal and neonatal pancreatic islet cell to glucose alone is due to a limited capacity to form cyclic AMP or to accelerated destruction of cyclic AMP by excessive phosphodiesterase activity or both remains to be demonstrated. The fetal and maternal plasma glucose and insulin, and the fetal growth hormone responses to the fetal administration of theophylline combined with either glucagon or glucose were examined in the subhuman primate fetus (Macaca mulatta) in late gestation. Theophylline enhanced and potentiated the fetal insulin responses to glucagon. Glucose combined with theophylline elicited a prompt rise in fetal plasma insulin, whereas glucose or theophylline alone did not. The neonate responded similarly to the combined theophylline and glucose injections with a prompt increase in plasma insulin levels. Fetal and neonatal plasma insulin levels were also promptly increased during the infusion of the dibutyryl derivative of cyclic 3′,5′ adenosine monophosphate to the fetus and neonate, respectively. Growth hormone levels were not altered in a consistent pattern during any of these experiments. These data indicate that the defect in the fetal and neonatal pancreatic betacell response to glucose is in the insulin releasing mechanism, rather than the synthesis of the hormone. Whether the apparent insensitivity of the fetal and neonatal pancreatic islet cell to glucose alone is due to a limited capacity to form cyclic AMP or to accelerated destruction of cyclic AMP by excessive phosphodiesterase activity or both remains to be demonstrated.