Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation

Carlson, C. J.; White, Morris F.; Rondinone, Cristina M.

doi:10.1016/j.bbrc.2004.02.082

Cited by 133 publications

(101 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular mechanism by which glutamine induced this tissue-specific insulin resistance is not completely known, but may be related to multiple mechanisms [2,43,44].…”

Section: Ementioning

confidence: 99%

RETRACTED ARTICLE:l-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis Diet-induced obesity (DIO) is associated with insulin resistance in liver and muscle, but not in adipose tissue. Mice with fat-specific disruption of the gene encoding the insulin receptor are protected against DIO and glucose intolerance. In cell culture, glutamine induces insulin resistance in adipocytes, but has no effect in muscle cells. We investigated whether supplementation of a highfat diet with glutamine induces insulin resistance in adipose tissue in the rat, improving insulin sensitivity in the whole animal.Materials and methods Male Wistar rats received standard rodent chow or a high-fat diet (HF) or an HF supplemented with alanine or glutamine (HFGln) for 2 months. Light microscopy and morphometry, oxygen consumption, hyperinsulinaemic-euglycaemic clamp and immunoprecipitation/ immunoblotting were performed. Results HFGln rats showed reductions in adipose mass and adipocyte size, a decrease in the activity of the insulininduced IRS-phosphatidylinositol 3-kinase (PI3-K)-protein kinase B-forkhead transcription factor box 01 pathway in adipose tissue, and an increase in adiponectin levels. These results were associated with increases in insulin-stimulated glucose uptake in skeletal muscle and insulin-induced suppression of hepatic glucose output, and were accompanied by an increase in the activity of the insulin-induced IRS-PI3-K-Akt pathway in these tissues. In parallel, there were decreases in TNFα and IL-6 levels and reductions in c-jun N-terminal kinase (JNK), IκB kinase subunit β (IKKβ) and mammalian target of rapamycin (mTOR) activity in the liver, muscle and adipose tissue. There was also an increase in oxygen consumption and a decrease in the respiratory exchange rate in HFGln rats. Conclusions/interpretation Glutamine supplementation induces insulin resistance in adipose tissue, and this is accompanied by an increase in the activity of the hexosamine pathway. It also reduces adipose mass, consequently attenuating insulin resistance and activation of JNK and IKKβ, while improving insulin signalling in liver and muscle.

show abstract

“…The molecular mechanism by which glutamine induced this tissue-specific insulin resistance is not completely known, but may be related to multiple mechanisms [2,43,44].…”

Section: Ementioning

confidence: 99%

RETRACTED ARTICLE:l-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Survival of ovarian cells has been reported to be at least partially dependent upon a functional PI3K signaling pathway (53, 54) Activation of mTOR/S6K1 signaling has been shown to suppress growth factor-dependent PI3K/AKT signaling through the phosphorylation and subsequent degradation of insulin receptor substrate proteins (55)(56)(57)(58). At the end of the luteal phase, the ability of PGF2␣ to activate mTOR/S6K1 (without a requirement for PI3K activation) suggests a mode of action by which PGF2␣ could compromise survival in the luteal cell by reducing PI3K/AKT signals and render the luteal cell susceptible to the actions of cytotoxic cytokines.…”

Section: Discussionmentioning

confidence: 99%

AKT-independent Phosphorylation of TSC2 and Activation of mTOR and Ribosomal Protein S6 Kinase Signaling by Prostaglandin F2α

Arvisais

Romanelli

Hou

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

The corpus luteum (CL)2 is a transient endocrine gland derived from an ovulated follicle within the ovary. The steroidogenic cells of the CL produce progesterone, a prerequisite for normal maintenance of pregnancy in mammals. In the event of pregnancy, the CL retains its role in progesterone synthesis in support of early pregnancy. In the absence of pregnancy luteolysis or corpus luteum regression occurs, a physiologic process associated with a reduction in progesterone secretion (functional regression) followed by death of endothelial and steroidogenic cells (structural regression) (1-4). Prostaglandin F2␣ (PGF2␣) was identified as a luteolytic factor over 35 years ago (5, 6). Recent genetic studies in mice lacking the PGF2␣ receptor (FP) further highlight the role for PGF2␣ in CL regression. Mice lacking FP receptors experience defects in CL regression and consequently parturition does not occur because of the maintenance of progesterone secretion at the end of pregnancy (7).The FP receptor is a member of the large class of heterotrimeric G-protein-coupled receptors (GPCRs) (8) and is present on the surface of steroidogenic luteal cells. PGF2␣ binding to its G q -coupled receptor results in activation of phospholipase ␤ (PLC␤) and consequent generation of the second messengers; diacylglycerol and inositol trisphosphate (9). The resultant increase in protein kinase C (PKC) activity in luteal cells contributes to the activation of other downstream protein kinases. PGF2␣ stimulates the activity of the extracellular signal-regulated kinase (Erk) family of mitogen-activated protein kinases (MAPK) through a mechanism that involves the PKC-dependent phosphorylation and activation of Raf (10, 11). These events result in the induction of early response genes that code for transcription factors that in turn, alter the synthesis of proteins that regulate progesterone synthesis (12-14). Little is understood regarding other signaling mechanisms initiated by PGF2␣ that account for the actions of PGF2␣ in the CL.The mammalian target of rapamycin (mTOR) protein is a key regulator of protein translation via mechanisms involving the phosphorylation of the translation regulator eukaryotic initiation factor 4E (eIF4E) -binding protein (4EBP1) and the 70-kDa ribosomal protein S6 protein kinase 1 (S6K1) (15,16 receptor; GPCR, G-protein-coupled receptor; mTOR, mammalian target of rapamycin; m 7 G, 7-methyl-guanosine; PI3K, phosphatidylinositol-3-kinase; PGF2␣, prostaglandin F2␣; S6K1, p70 ribosomal S6 kinase; TSC2, tuberous sclerosis complex 2; FBS, fetal bovine serum; FCS, fetal calf serum; JNK, c-Jun N-terminal kinase; PMA, phorbol 12-myristate 13-acetate; PKC, protein kinase C.

show abstract

“…Rapamycin treatment has been shown to inhibit phosphorylation of IRS-1 on Ser-307, Ser-312, Ser-612, and Ser-636/639 (human notation of IRS-1 Ser residues) (11,12,23,24,27,28). Of these residues, mTOR has been shown to directly catalyze the phosphorylation of Ser-636/639 (11), whereas S6K1 was shown to phosphorylate Ser-307 (mouse Ser-302) in vitro (12).…”

mentioning

confidence: 99%

Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance

Tremblay

Brûlé

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

401

329

View full text Add to dashboard Cite

show abstract

Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation

Cited by 133 publications

References 32 publications

RETRACTED ARTICLE:l-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity

RETRACTED ARTICLE:l-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity

AKT-independent Phosphorylation of TSC2 and Activation of mTOR and Ribosomal Protein S6 Kinase Signaling by Prostaglandin F2α

Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance

Contact Info

Product

Resources

About