Hyperglycemia-Induced Oxidative-Nitrosative Stress Induces Inflammation & Neurodeg...
 

I have been trying to track down studies which show the progression of hyperglycemia to problems of the sclerosis type.

I found this:

https://link.springer.com/article/1...2035-015-9667-3

Molecular Neurobiology
January 2017, Volume 54, Issue 1, pp 238–254

Hyperglycemia-Induced Oxidative-Nitrosative Stress Induces Inflammation and Neurodegeneration via Augmented Tuberous Sclerosis Complex-2 (TSC-2) Activation in Neuronal Cells

Authors
Premranjan Kumar, Thiagarajan Raman, Mitali Madhusmita Swain, Rangnath Mishra, Arttatrana Pal.

Article
First Online: 06 January 2016

Abstract
Diabetes is a systemic disease mainly characterized by chronic hyperglycemia and with extensive and long-lasting spiteful complications in central nervous systems (CNS). Astrocytes play an important role in the defense mechanism of CNS, with great ability of withstanding accumulation of toxic substances.

Apart from functional disorders, hyperglycemia leads to slow progressive structural abnormalities in the CNS through oxidative stress pathways. However, the molecular mechanism by which neurons die under oxidative stress induced by high glucose (HG) remains largely unclear. Here, we report that HG-induced inflammation and neurodegeneration in brain tissues, brain astrocytes (C6), and pheochromocytoma (PC-12) cells are cultured in HG conditions.

Our results show that the increases in phosphorylation of Akt and ERK1/2MAPK are associated with increased accumulations of reactive oxygen species (ROS) in neuronal cells, which simultaneously enhanced phosphorylations of tuberous sclerosis complex-2 (TSC-2) and mammalian target of rapamycin (mTOR) in the diabetic brain and in HG-exposed neuronal cells. Pharmacologic inhibition of Akt or ERK1/2 or siRNA-mediated gene silencing of TSC-2 suppressed the strong downregulation of TSC-2-mTOR activation. Findings of this study also demonstrate that HG resulted in phosphorylation of NF-κB, coinciding with the increased production of inflammatory mediators and activation of neurodegenerative markers.

Pretreatment of cells with antioxidants, phosphoinositide3-kinase (PI3-K)/Akt, and ERK1/2 inhibitors significantly reduced HG-induced TSC-2 phosphorylation and restored NF-κB protein expression leading to decreased production of inflammatory mediators and neurodegenerative markers.

These results illustrate that ROS functions as a key signaling component in the regulatory pathway induced by elevated glucose in neuronal cell activation leading to inflammation and neurodegeneration.

Keywords

Oxidative stress Neuronal cells Tuberous sclerosis complex-2 Apoptosis Inflammation Neurodegeneration


The full-text is by purchase.

To me, this is another example showing how people such as Dr. John Yudkin, Dr. Jan Kwasniewski and Dr. Ron Rosedale are right regarding the necessity to eat low carb, adequate protein, and high fat.

Dr. Rosedale is the only one I know of who addresses how too much protein causes mTOR problems.

Here is the transcript of Robb Wolf interview Dr. Rosedale:

http://robbwolf.com/wp-content/uplo...olution-350.pdf

Interview can be heard at:

https://robbwolf.com/2017/01/17/epi...b-and-diabetes/

Dr. Rosedale's site:

http://drrosedale.com/#axzz5nzyqIsjQ

In the new book by Patrick Holford & Jerome Burne "The Hybrid Diet" there is a thorough explanation about mTOR & too much protein