Could Someone Explain How Inflammation Causes Diabetes (metabolic Disease) On Cell Level

[Kingpinguin]

Hi!
I’m new around here.
Trying to grasp how inflammation on a cellular level causes specifically insulin resistance.
Id like to know so I can explain it further.
So you need to consume sugars. And insulin needs to be produced to push that sugar in to your cells so they can create energy. If we would introduce something very inflammatory such has PUFA (arachidonic acid) without enough antioxidants inplace over an extended period of time how does the oxidising effect block the mechanism of insulin delivering glucose to the cells? Or how does it work? I’d like to know in as great detail as possible.
Thanks in advance!

 

[Kingpinguin]

Anyone?

 

[DrJ]

Did you read this one?

Diabetes, scleroderma, oils and hormones

It's pretty good.

 

[Kingpinguin]

Did you read this one?

Diabetes, scleroderma, oils and hormones

It's pretty good.

Skimmed through it. Didnt really go into detail only explained stuff I already knew. You ingest glucose insulin is secreted to shuttle it to the cell for energy. I understand pufa hinders cellular respiration through inflammation. But ok so arachidonic acid comes along and activates prostaglandins. Excess prostaglandins and it activation does what to the mitochondria? Does it bind to it and inhibit it? Does it signal the mitochondria to slow down? What enzymes, proteins etc are involved with that? We can say pufa causes inflammation and inflammation wrecks mitochondria. A kid would ask how exactly? And an adult would answer i don’t know thats just how it is. Well there has to be an answer. What does prostaglandins do to the cell to make it not absorb glucose as effectivly?

 

[Kingpinguin]

Did you read this one?

Diabetes, scleroderma, oils and hormones

It's pretty good.

Regulation of pancreatic β-cell function and mass dynamics by prostaglandin signaling

Something more like this. But I would like a clearer picture. Im not intelligent enough to understand it all so well so would be helpfull if anyone knew the answer and could explain it simply. I want to know so that I can help others and explain why PUFA is bad and causes diabetes. If you just tell your parents PUFA causes diabetes they first go what is PUFA? Then you go ah its like canola oil. Then they laugh and be like yeah right sugar causes diabetes not canola oil.

 

[Kingpinguin]

Did you read this one?

Diabetes, scleroderma, oils and hormones

It's pretty good.

https://www.sciencedirect.com/science/article/abs/pii/S1521690X06000789

Inflammatory molecules and lipid metabolites inhibit insulin signalling by stimulating a number of different serine kinases which are responsible for serine phosphorylation of Insulin Receptor Substrate-1 (IRS-1).

IRS1 - Wikipedia

Function
Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 (IGF-1) receptors to intracellular pathways PI3K / Akt and Erk MAP kinase pathways.

Different Serine phosphorylation of IRS-1, caused by various molecules, such as fatty acids, TNFα and AMPK, has different effects on the protein, but most of these effects include cellular re-localization, conformational and steric changes. These processes lead to decrease in Tyrosine phosphorylation by insulin receptors and diminished PI3K recruitment. Altogether, these mechanisms stimulate IRS-1 degradation and insulin resistance.

During insulin resistance induced by hyperglycemia, glucose accumulates in tissues as its hexosaminemetabolite UDP-GlcNAc. This metabolite if present in high amounts leads to O-GlcNAc protein modifications. IRS-1 can undergo this modification, which results in its phosphorylation and functional suppression.

IRS-1, as a signalling adapter protein, is able to integrate different signalling cascades, which indicates its possible role in cancer progression.[36] IRS-1 protein is known to be involved in various types of cancer, including colorectal,[37] lung,[38] prostate and breast cancer.

 

[milkboi]

One explanation I‘ve heard somewhere outside outside of this forum is that the mitochondrion basically gets stretched out by inflammation and that the electron transport chain works best if it is as compact as possible (less room between the different electron acceptors, so no electrons get lost between them). This made intuitive sense to me, but I‘m basically at high school level when it comes to biochemistry, so please be kind.

 

[Kingpinguin]

One explanation I‘ve heard somewhere outside outside of this forum is that the mitochondrion basically gets stretched out by inflammation and that the electron transport chain works best if it is as compact as possible (less room between the different electron acceptors, so no electrons get lost between them). This made intuitive sense to me, but I‘m basically at high school level when it comes to biochemistry, so please be kind.

Makes sense. Cell swelling is the first indication of cellular stress/injury. Appreciate your input.