scholarly journals Curcumin ameliorates insulin signalling pathway in brain of Alzheimer’s disease transgenic mice

2016 ◽  
Vol 29 (4) ◽  
pp. 734-741 ◽  
Author(s):  
Hui-li Feng ◽  
Hui-zi Dang ◽  
Hui Fan ◽  
Xiao-pei Chen ◽  
Ying-xue Rao ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transgenic Mice ◽  
Insulin Receptor ◽  
Insulin Signalling ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Brain Insulin ◽  
Insulin Signal Transduction Pathway

Deficits in glucose, impaired insulin signalling and brain insulin resistance are common in the pathogenesis of Alzheimer’s disease (AD); therefore, some scholars even called AD type 3 diabetes mellitus. Curcumin can reduce the amyloid pathology in AD. Moreover, it is a well-known fact that curcumin has anti-oxidant and anti-inflammatory properties. However, whether or not curcumin could regulate the insulin signal transduction pathway in AD remains unclear. In this study, we used APPswe/PS1dE9 double transgenic mice as the AD model to investigate the mechanisms and the effects of curcumin on AD. Immunohistochemical (IHC) staining and a western blot analysis were used to test the major proteins in the insulin signal transduction pathway. After the administration of curcumin for 6 months, the results showed that the expression of an insulin receptor (InR) and insulin receptor substrate (IRS)-1 decreased in the hippocampal CA1 area of the APPswe/PS1dE9 double transgenic mice, while the expression of phosphatidylinositol-3 kinase (PI3K), phosphorylated PI3K (p-PI3K), serine-threonine kinase (AKT) and phosphorylated AKT (p-AKT) increased. Among the curcumin groups, the medium-dose group was the most effective one. Thus, we believe that curcumin may be a potential therapeutic agent that can regulate the critical molecules in brain insulin signalling pathways. Furthermore, curcumin could be adopted as one of the AD treatments to improve a patient’s learning and memory ability.

Discovery of PDKI, One of the Missing Links in Insulin Signal Transduction

2001 ◽  
Vol 29 (2) ◽  
pp. 1-14 ◽  
Author(s):  
D. R. Alessi
Keyword(s):  
Signal Transduction ◽  
Insulin Signalling ◽  
Glycogen Synthesis ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Insulin Signalling Pathway ◽  
Treatment Of Diabetes ◽  
Insulin Signal Transduction Pathway

Historically, two strategies have been used to dissect the insulin signal transduction pathway. One was to start at the insulin receptor and work down the signal transduction pathway from the plasma membrane. The other was to select a physiological action of insulin, namely the mechanism by which insulin stimulates glycogen synthesis, and then work backwards towards the receptor. The hope was that eventually the groups working down from the top of the insulin signalling pathway would meet up with those working upwards from the bottom of the pathway. This has now happened, and in this lecture I will describe the recent advances that have linked the research from both ends of the insulin signal transduction pathway. I will also discuss how these findings have enabled pharmaceutical companies to embark on novel programmes to develop improved therapies for the treatment of diabetes in the future.

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 PI3 kinase directly phosphorylates Akt1/2 at Ser473/474 in the insulin signal transduction pathway

2013 ◽  
Vol 220 (1) ◽  
pp. 49-59 ◽  
Author(s):  
A Tsuchiya ◽  
T Kanno ◽  
T Nishizaki
Keyword(s):  
Signal Transduction ◽  
Glucose Transporter ◽  
Signal Transduction Pathway ◽  
Significant Inhibition ◽  
Dependent Manner ◽  
Transduction Pathway ◽  
Glut4 Translocation ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Insulin Signal Transduction Pathway

Insulin stimulated translocation of the glucose transporter GLUT4 from the cytosol to the plasma membrane in a concentration (1 nM–1 μM)-dependent manner and increased glucose uptake in 3T3-L1 adipocytes. Insulin-induced GLUT4 translocation to the cell surface was prevented by the phosphoinositide 3 kinase (PI3K) inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase 1 (PDK1) inhibitor BX912 or the Akt1/2 inhibitor MK2206, and by knocking-down PI3K, PDK1 or Akt1/2. Insulin increased phosphorylation of Akt1/2 at Thr308/309 and Ser473/474, to activate Akt1/2, in the adipocytes. Insulin-induced phosphorylation of Akt1/2 was suppressed by wortmannin and knocking-down PI3K, while no significant inhibition of the phosphorylation was obtained with BX912 or knocking-down PDK1. In the cell-free Akt assay, PI3K phosphorylated Akt1 both at Thr308 and Ser473 and Akt2 at Ser474 alone. In contrast, PDK1 phosphorylates Akt1 at Thr308 and Akt2 at Thr309. The results of this study indicate that PI3K activates Akt1, independently of PDK1, and Akt2 by cooperating with PDK1 in the insulin signal transduction pathway linked to GLUT4 translocation.

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