title: Augmentation of insulin secretion by leucine supplementation in malnourished rats: possible involvement of the phosphatidylinositol 3-phosphate kinase/mammalian target protein of rapamycin pathway.
abstract: A regimen of low-protein diet induces a reduction of pancreatic islet function that is associated with development of metabolic disorders including diabetes and obesity afterward. In the present study, the influence of leucine supplementation on metabolic parameters, insulin secretion to glucose and to amino acids, as well as the levels of proteins that participate in the phosphatidylinositol 3-phosphate kinase (PI3K) pathway was investigated in malnourished rats. Four groups were fed with different diets for 12 weeks: a normal protein diet (17%) without (NP) or with leucine supplementation (NPL) or a low (6%)-protein diet without (LP) or with leucine supplementation (LPL). Leucine was given in the drinking water during the last 4 weeks. As indicated by the intraperitoneal glucose tolerance test, LPL rats exhibited increased glucose tolerance as compared with NPL group. Both NPL and LPL rats had higher circulating insulin levels than controls. The LPL rats also showed increased insulin secretion by pancreatic islets in response to glucose or arginine compared with those observed in islets from LP animals. Glucose oxidation was significantly reduced in NPL, LP, and LPL isolated islets as compared with NP; but no alteration was observed for leucine and glutamate oxidation among the 4 groups. Western blotting analysis demonstrated increased PI3K and mammalian target protein of rapamycin protein contents in LPL compared with LP islets. A significant increase in insulin-induced insulin receptor substrate 1-associated PI3K activation was also observed in LPL compared with LP islets. These findings indicate that leucine supplementation can augment islet function in malnourished rats and that activation of the PI3K/mammalian target protein of rapamycin pathway may play a role in this process.
authors.affiliation: Department of Anatomy, Cell Biology and Physiology and Biophysics, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Eliane
authors.initials: E
authors.lastname: Filiputti
authors.forename: Alex
authors.initials: A
authors.lastname: Rafacho
authors.forename: Eliana P
authors.initials: EP
authors.lastname: Araújo
authors.forename: Leonardo R
authors.initials: LR
authors.lastname: Silveira
authors.forename: Amon
authors.initials: A
authors.lastname: Trevisan
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Batista
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Lício A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Boschero
authors.forename: Everardo M
authors.initials: EM
authors.lastname: Carneiro
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D019587:Dietary Supplements; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage*; D008297:Male; D044342:Malnutrition / Q000188:drug therapy / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
chemical_list: D001798:Blood Proteins; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D018129:Phosphatidylinositol Phosphates; C055525:phosphatidylinositol 3-phosphate; D012313:RNA; C546845:mTOR protein, rat; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D058570:TOR Serine-Threonine Kinases; D007930:Leucine