In vivo evidence that insulin does not inhibit hepatic tryptophan pyrrolase activity in rats.
Previous reports have indicated that insulin administration triggers an early increase in plasma tryptophan (TRP) levels in fasted rats. Then, the present study was undertaken to investigate the putative role of liver tryptophan pyrrolase (TPO) in this short-term effect of insulin. In 24 hr fasted rats, doses of insulin that triggered an increase in plasma TRP levels (i.e., 2-3 I.U./kg, 1 hr) did not alter either holoenzyme or total enzyme activity. In another series of experiments, the administration of insulin (2 I.U./kg) to 24 hr fasted rats promoted biphasic time effects on plasma TRP levels and liver TPO activity. Thus, insulin initially triggered a rise in plasma TRP (without any change in liver TPO activity) and then increased liver TPO activity whilst plasma TRP returned toward control levels. In addition, hypercorticosteronemia was evidenced throughout the first phasis. Lastly, the influence of insulin administration (2 I.U./kg) on fasting-induced TPO induction was analysed. Whereas fasting increased liver TPO activity in a time-dependent manner, insulin administration (2 I.U./kg, 30 min) did not modify either plasma TRP or liver TPO activity. The data reported herein bring evidence that the effect of insulin administration on circulating TRP is not mediated by an inhibition of hepatic TPO.
Laboratoire de Pharmacologie, INSERM U7, CHU Necker - E.M., Paris, France.
P
P
Broqua
V
V
Baudrie
D
D
Laude
Y
Y
Guezennec
F
F
Chaouloff
D000818:Animals; D003345:Corticosterone / Q000097:blood; D005215:Fasting; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000097:blood; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors*
D007328:Insulin; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D003345:Corticosterone