scholarly journals Direct Cross-talk of Interleukin-6 and Insulin Signal Transduction via Insulin Receptor Substrate-1 in Skeletal Muscle Cells

2006 ◽  
Vol 281 (11) ◽  
pp. 7060-7067 ◽  
Author(s):  
Cora Weigert ◽  
Anita M. Hennige ◽  
Rainer Lehmann ◽  
Katrin Brodbeck ◽  
Frank Baumgartner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signal Transduction ◽  
Insulin Receptor ◽  
Cross Talk ◽  
Interleukin 6 ◽  
Muscle Cells ◽  
Insulin Receptor Substrate ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Direct Cross

Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle

2005 ◽  
Vol 288 (2) ◽  
pp. R473-R481 ◽  
Author(s):  
Marianne S. Anderson ◽  
M. Thamotharan ◽  
Doris Kao ◽  
Sherin U. Devaskar ◽  
Liping Qiao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signal Transduction ◽  
Insulin Receptor ◽  
Mrna Translation ◽  
Insulin Concentration ◽  
Fetal Sheep ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Signal Transduction Proteins ◽  
Ovine Fetal

To test the effects of acute fetal hyperinsulinemia on the pattern and time course of insulin signaling in ovine fetal skeletal muscle, we measured selected signal transduction proteins in the mitogenic, protein synthetic, and metabolic pathways in the skeletal muscle of normally growing fetal sheep in utero. In experiment 1, 4-h hyperinsulinemic-euglycemic clamps were conducted in anesthetized twin fetuses to produce selective fetal hyperinsulinemia-euglycemia in one twin and euinsulinemia-euglycemia in the other. Serial skeletal muscle biopsies were taken from each fetus during the clamp and assayed by Western blot for selected insulin signal transduction proteins. Tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and the p85 subunit of phosphatidylinositol 3-kinase doubled at 30 min and gradually returned to control values by 240 min. Phosphorylation of extracellular signal-regulated kinase 1,2 was increased fivefold through 120 min of insulin infusion and decreased to control concentration by 240 min. Protein kinase B phosphorylation doubled at 30 min and remained elevated throughout the study. Phosphorylation of p70 S6K increased fourfold at 30, 60, and 120 min. In the second experiment, a separate group of nonanesthetized singleton fetuses was clamped to intermediate and high hyperinsulinemic-euglycemic conditions for 1 h. GLUT4 increased fourfold in the plasma membrane at 1 h, and hindlimb glucose uptake increased significantly at the higher insulin concentration. These data demonstrate that an acute increase in fetal plasma insulin concentration stimulates a unique pattern of insulin signal transduction proteins in intact skeletal muscle, thereby increasing pathways for mRNA translation, glucose transport, and cell growth.

Delaying of insulin signal transduction in skeletal muscle cells by selenium compounds

2011 ◽  
Vol 105 (6) ◽  
pp. 812-820 ◽  
Author(s):  
Antonio Pinto ◽  
Bodo Speckmann ◽  
Martin Heisler ◽  
Helmut Sies ◽  
Holger Steinbrenner
Keyword(s):  
Skeletal Muscle ◽  
Signal Transduction ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Selenium Compounds ◽  
Insulin Signal Transduction ◽  
Insulin Signal

scholarly journals Signal Transducer and Activator of Transcription (Stat)-Induced Stat Inhibitor 1 (Ssi-1)/Suppressor of Cytokine Signaling 1 (Socs1) Inhibits Insulin Signal Transduction Pathway through Modulating Insulin Receptor Substrate 1 (Irs-1) Phosphorylation

2001 ◽  
Vol 193 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yoshinori Kawazoe ◽  
Tetsuji Naka ◽  
Minoru Fujimoto ◽  
Hidetsugu Kohzaki ◽  
Yoshiaki Morita ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Negative Feedback ◽  
Signal Transduction Pathway ◽  
Cytokine Signaling ◽  
Insulin Receptor Substrate ◽  
Signal Transducer ◽  
Transduction Pathway ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Insulin Signal Transduction Pathway

Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1–deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin. Furthermore, SSI-1 achieves this inhibition both by binding directly to IRS-1 and by suppressing Janus kinases. These findings suggest that SSI-1 acts as a negative feedback factor also in the insulin signal transduction pathway through the suppression of IRS-1 phosphorylation.

scholarly journals Insulin Signal Transduction by a Mutant Human Insulin Receptor Lacking the NPEY Sequence

1997 ◽  
Vol 272 (36) ◽  
pp. 22884-22890 ◽  
Author(s):  
Paulos Berhanu ◽  
Celia Anderson ◽  
Matt Hickman ◽  
Theodore P. Ciaraldi
Keyword(s):  
Signal Transduction ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Human Insulin Receptor

scholarly journals Interplay and Effects of Temporal Changes in the Phosphorylation State of Serine-302, -307, and -318 of Insulin Receptor Substrate-1 on Insulin Action in Skeletal Muscle Cells

2008 ◽  
Vol 22 (12) ◽  
pp. 2729-2740 ◽  
Author(s):  
Cora Weigert ◽  
Matthias Kron ◽  
Hubert Kalbacher ◽  
Ann Kathrin Pohl ◽  
Heike Runge ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Insulin Action ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Insulin Signal ◽  
Kinase C ◽  
Phosphorylation Pattern

Abstract Transduction of the insulin signal is mediated by multisite Tyr and Ser/Thr phosphorylation of the insulin receptor substrates (IRSs). Previous studies on the function of single-site phosphorylation, particularly phosphorylation of Ser-302, -307, and -318 of IRS-1, showed attenuating as well as enhancing effects on insulin action. In this study we investigated a possible cross talk of these opposedly acting serine residues in insulin-stimulated skeletal muscle cells by monitoring phosphorylation kinetics, and applying loss of function, gain of function, and combination mutants of IRS-1. The phosphorylation at Ser-302 was rapid and transient, followed first by Ser-318 phosphorylation and later by phosphorylation of Ser-307, which remained elevated for 120 min. Mutation of Ser-302 to alanine clearly reduced the subsequent protein kinase C-ζ-mediated Ser-318 phosphorylation. The Ser-307 phosphorylation was independent of Ser-302 and/or Ser-318 phosphorylation status. The functional consequences of these phosphorylation patterns were studied by the expression of IRS-1 mutants. The E302A307E318 mutant simulating the early phosphorylation pattern resulted in a significant increase in Akt and glycogen synthase kinase 3 phosphorylation. Furthermore, glucose uptake was enhanced. Because the down-regulation of the insulin signal was not affected, this phosphorylation pattern seems to be involved in the enhancement but not in the termination of the insulin signal. This enhancing effect was completely absent when Ser-302 was unphosphorylated and Ser-307 was phosphorylated as simulated by the A302E307E318 mutant. Phospho-Ser-318, sequentially phosphorylated at least by protein kinase C-ζ and a mammalian target of rapamycin/raptor-dependent kinase, was part of the positive as well as of the subsequent negative phosphorylation pattern. Thus we conclude that insulin stimulation temporally generates different phosphorylation statuses of the same residues that exert different functions in insulin signaling.

scholarly journals The NAD(P)H Oxidase Homolog Nox4 Modulates Insulin-Stimulated Generation of H2O2 and Plays an Integral Role in Insulin Signal Transduction

2004 ◽  
Vol 24 (5) ◽  
pp. 1844-1854 ◽  
Author(s):  
Kalyankar Mahadev ◽  
Hiroyuki Motoshima ◽  
Xiangdong Wu ◽  
Jean Marie Ruddy ◽  
Rebecca S. Arnold ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Insulin Action ◽  
Protein Tyrosine Phosphatases ◽  
Cellular Protein ◽  
Dominant Negative ◽  
Target Cells ◽  
Insulin Signal Transduction ◽  
Insulin Signal

ABSTRACT Insulin stimulation of target cells elicits a burst of H2O2 that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated H2O2 generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation, activation of downstream serine kinases, and glucose uptake. Transfection of specific small interfering RNA oligonucleotides reduced Nox4 protein abundance and also inhibited the insulin signaling cascade. Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated IR tyrosine phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic activity. These data suggest that Nox4 provides a novel link between the IR and the generation of cellular reactive oxygen species that enhance insulin signal transduction, at least in part via the oxidative inhibition of cellular protein-tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been previously implicated in the regulation of insulin action.

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