microRNA‐206 is required for osteoarthritis development through its effect on apoptosis and autophagy of articular chondrocytes via modulating the phosphoinositide 3‐kinase/protein kinase B‐mTOR pathway by targeting insulin‐like growth factor‐1

2018 ◽  
Vol 120 (4) ◽  
pp. 5287-5303 ◽  
Author(s):  
Qian Yu ◽  
Bei Zhao ◽  
Qi He ◽  
Yuan Zhang ◽  
Xian‐Bo Peng
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Articular Chondrocytes ◽  
Protein Kinase B ◽  
Mtor Pathway ◽  
Insulin Like Growth Factor ◽  
Phosphoinositide 3 Kinase

scholarly journals Vitamin D3 Activates Phosphatidylinositol-3-Kinase/Protein Kinase B via Insulin-Like Growth Factor-1 to Improve Testicular Function in Diabetic Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yanyan He ◽  
Yang Liu ◽  
Qing-Zhu Wang ◽  
Feng Guo ◽  
Fengjuan Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Diabetic Rats ◽  
Testicular Function ◽  
Insulin Like Growth Factor ◽  
Wild Type ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Objective. In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. Materials and Methods. Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 μg/kg/day), high (0.1 μg/kg/day), and high (0.1 μg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 μg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. Results. Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. Conclusions. The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.

scholarly journals Mechanical stimuli regulate rapamycin-sensitive signalling by a phosphoinositide 3-kinase-, protein kinase B- and growth factor-independent mechanism

2004 ◽  
Vol 380 (3) ◽  
pp. 795-804 ◽  
Author(s):  
Troy A. HORNBERGER ◽  
Rudy STUPPARD ◽  
Kevin E. CONLEY ◽  
Mark J. FEDELE ◽  
Marta L. FIOROTTO ◽  
...  
Keyword(s):  
Growth Factors ◽  
Protein Kinase ◽  
Mechanical Load ◽  
Ex Vivo ◽  
Protein Kinase B ◽  
Mtor Pathway ◽  
Central Component ◽  
Translational Efficiency ◽  
Mechanical Stimuli ◽  
Phosphoinositide 3 Kinase

In response to growth factors, mTOR (mammalian target of rapamycin) has been identified as a central component of the signalling pathways that control the translational machinery and cell growth. Signalling through mTOR has also been shown to be necessary for the mechanical load-induced growth of cardiac and skeletal muscles. Although the mechanisms involved for mechanically induced activation of mTOR are not known, it has been suggested that activation of PI3K (phosphoinositide 3-kinase) and protein kinase B (Akt), via the release of locally acting growth factors, underlies this process. In the present study, we show that mechanically stimulating (passive stretch) the skeletal muscle ex vivo results in the activation of mTOR-dependent signalling events. The activation of mTOR-dependent signalling events was necessary for an increase in translational efficiency, demonstrating the physiological significance of this pathway. Using pharmacological inhibitors, we show that activation of mTOR-dependent signalling occurs through a PI3K-independent pathway. Consistent with these results, mechanically induced signalling through mTOR was not disrupted in muscles from Akt1−/− mice. In addition, ex vivo co-incubation experiments, along with in vitro conditioned-media experiments, demonstrate that a mechanically induced release of locally acting autocrine/paracrine growth factors was not sufficient for the activation of the mTOR pathway. Taken together, our results demonstrate that mechanical stimuli can activate the mTOR pathway independent of PI3K/Akt1 and locally acting growth factors. Thus mechanical stimuli and growth factors provide distinct inputs through which mTOR co-ordinates an increase in the translational efficiency.

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