Augmentation of insulin secretion by leucine supplementation in malnourished rats: possible involvement of the phosphatidylinositol 3-phosphate kinase/mammalian target protein of rapamycin pathway

被引：37

作者：

Filiputti, Eliane ^{[1
]}

Rafacho, Alex ^{[1
,2
]}

Araujo, Eliana P. ^{[1
,2
]}

Silveira, Leonardo R. ^{[3
]}

Trevisan, Amon ^{[1
,2
]}

Batista, Thiago M. ^{[1
,2
]}

Curi, Rui ^{[2
,4
]}

Velloso, Licio A. ^{[1
,2
]}

Quesada, Ivan ^{[5
,6
]}

Boschero, Antonio C. ^{[1
,2
]}

Carneiro, Everardo M. ^{[1
,2
]}

机构：

[1] Univ Estadual Campinas, UNICAMP, Dept Anat Cell Biol & Physiol & Biophys, Inst Biol, BR-13083970 Campinas, SP, Brazil

[2] Natl Inst Obes & Diabet, BR-13083970 Campinas, SP, Brazil

[3] Univ Sao Paulo, Sch Phys Educ & Sports, BR-14040900 Ribeirao Preto, SP, Brazil

[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, Brazil

[5] Univ Miguel Hernandez, CIBERDEM, Elche 03202, Spain

[6] Univ Miguel Hernandez, Inst Bioengn, Elche 03202, Spain

来源：

METABOLISM-CLINICAL AND EXPERIMENTAL | 2010年 / 59卷 / 05期

基金：

巴西圣保罗研究基金会;

关键词：

PANCREATIC BETA-CELLS; GENE-EXPRESSION; RECEPTOR SUBSTRATE-1; METABOLIC-REGULATION; AUTOCRINE REGULATION; ENDOCRINE PANCREAS; SIGNALING PATHWAY; CA2+ HOMEOSTASIS; ALPHA EXPRESSION; DEFICIENT RATS;

D O I：

10.1016/j.metabol.2009.09.007

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 I 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/maminalian target protein of rapamycin pathway may play a role in this process. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：635 / 644

页数：10

共 56 条

[1]

Amaral MEC, 2003, HORM METAB RES, V35, P282

[2] Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2 [J].