Lysosomal and proteasome-dependent proteolysis are differentially regulated by insulin and/or amino acids following feeding in young, mature and old rats.
Skeletal muscle proteolysis is inhibited by oral feeding in the young and mature but not in the elderly. However, the proteolytic pathway(s) responsible for the decreased muscle proteolysis in the postprandial (PP) state is (are) unknown in the young. Moreover, muscle proteolysis is inhibited by both insulin (INS) and amino acids (AA) in vitro, but their respective roles on specific proteolytic pathways in vivo remain to be elucidated. The aim of this study was to investigate the respective role of INS and AA on the inhibition of proteolytic pathways in the PP state in skeletal muscles from young, mature and old rats. Rats were fed over 1 h either a 25% (AA+) or a 0% (AA-) amino acid/protein meal. In each nutritional condition, PP insulin secretion was maintained (AA+/INS+ and AA-/INS+) or blocked (AA+/INS- and AA-/INS-) with diazoxide injections. We report that the PP inhibition of proteolysis in young rats was mediated by the increased INS secretion and resulted from a down-regulation of both lysosomal and Ca(2+)-dependent proteolysis. Moreover, our data showed that proteasome activities are inhibited by either INS or AA in mature rats, whereas they become selectively insensitive to AA in old rats. In conclusion, the present work provides direct evidence that the lack of PP regulation of proteasome-dependent proteolysis in old rats resulted from a selective resistance to AA.
Capel
Frédéric
F
INRA, Centre Clermont-Ferrand-Theix, UMR1019, Unité de Nutrition Humaine, St Genes Champanelle, F-63122 France.
Prod'homme
Magalie
M
Béchet
Daniel
D
Taillandier
Daniel
D
Balage
Michèle
M
Attaix
Didier
D
Combaret
Lydie
L
D000375:Aging; D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000008:administration & dosage; D004435:Eating / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D000078790:Insulin Secretion; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D019518:Postprandial Period; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D004044:Dietary Proteins; D007328:Insulin; D007329:Insulin Antagonists; D011506:Proteins; D046988:Proteasome Endopeptidase Complex; D003981:Diazoxide