Endocrine and amino acid regulation of liver macroautophagy and proteolytic function.

Regulation of liver macroautophagy and protein degradation by hormones and direct regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels and glutamine release from the perfused liver. Autophagic vacuoles were observed in the pericanalicular area of liver cells after 30 min. Levels and release of other regulatory amino acids did not exhibit any significant decrease but subsequently increased. Intraperitoneal administration of glutamine inhibited the proteolytic response. In conclusion, these studies demonstrate that in vivo induction and control of liver macroautophagy and protein degradation by the physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and asynchronous changes in the levels of selected direct regulatory amino acids (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine levels).