title: Acute rapamycin treatment improved glucose tolerance through inhibition of hepatic gluconeogenesis in rainbow trout (Oncorhynchus mykiss).
abstract: Our aim was to investigate the potential role of TOR (target of rapamycin) signaling pathway in the regulation of hepatic glucose metabolism in rainbow trout. Fasted fish were first treated with a single intraperitoneal injection of rapamycin or vehicle and then submitted to a second intraperitoneal administration of glucose 4 h later. Our results revealed that intraperitoneal administration of glucose induced hyperglycemia for both vehicle and rapamycin treatments, which peaked at 2 h. Plasma glucose level in vehicle-treated fish was significantly higher than in rapamycin-treated fish at 8 and 17 h, whereas it remained at the basal level in rapamycin-treated fish. Glucose administration significantly enhanced the phosphorylation of Akt and ribosomal protein S6 kinase (S6K1) in vehicle-treated fish, while rapamycin completely abolished the activation of S6K1 in rapamycin-treated fish, without inhibiting the phosphorylation of Akt on Thr-308 or Ser-473. Despite the lack of significant variation in phosphoenolpyruvate carboxykinase mRNA abundance, mRNA abundance for glucokinase (GK), glucose 6-phosphatase (G6Pase) I and II, and fructose 1,6-bisphosphatase (FBPase) was reduced by rapamycin 17 h after glucose administration. The inhibition effect of rapamycin on GK and FBPase was further substantiated at the activity level. The suppression of GK gene expression and activity by rapamycin provided the first in vivo evidence in fish that glucose regulates hepatic GK gene expression and activity through a TORC1-dependent manner. Unlike in mammals, we observed that acute rapamycin treatment improved glucose tolerance through the inhibition of hepatic gluconeogenesis in rainbow trout.
authors.affiliation: Institut National de la Recherche Agronomique, UR 1067 Nutrition Métabolisme, Aquaculture, Pole d'Hydrobiologie, CD 918, Saint-Pée-sur-Nivelle, France.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Dai
authors.affiliation: Institut National de la Recherche Agronomique, UR 1067 Nutrition Métabolisme, Aquaculture, Pole d'Hydrobiologie, CD 918, Saint-Pée-sur-Nivelle, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Panserat
authors.affiliation: Institut National de la Recherche Agronomique, UR 1067 Nutrition Métabolisme, Aquaculture, Pole d'Hydrobiologie, CD 918, Saint-Pée-sur-Nivelle, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Terrier
authors.affiliation: Institut National de la Recherche Agronomique, UR 1067 Nutrition Métabolisme, Aquaculture, Pole d'Hydrobiologie, CD 918, Saint-Pée-sur-Nivelle, France.
authors.forename: Iban
authors.initials: I
authors.lastname: Seiliez
authors.affiliation: Institut National de la Recherche Agronomique, UR 1067 Nutrition Métabolisme, Aquaculture, Pole d'Hydrobiologie, CD 918, Saint-Pée-sur-Nivelle, France skiba@st-pee.inra.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Skiba-Cassy
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D029941:Fish Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006597:Fructose-Bisphosphatase / Q000235:genetics / Q000378:metabolism; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D017686:Oncorhynchus mykiss; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D029941:Fish Proteins; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D005941:Glucokinase; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D006597:Fructose-Bisphosphatase; D020123:Sirolimus
keywords: glucokinase; gluconeogenesis; glucose homeostasis; rainbow trout; rapamycin; target of rapamycin