This paper
presents one of the most fundamental concepts necessary to understand what insulin resistance actually means. I may have mentioned this (many times) before.
If you read nothing else from this paper, the discussion is essential. It's short. Without understanding this concept there is no hope of understanding what insulin resistance really is and you are left with bizarre concept of trying to "cure" it. As the authors say:
"In summary, the fact that mitochondrial O2•− is upstream of IR is of major significance suggesting that IR may be part of the antioxidant defense mechanism to protect cells from further oxidative damage. Thus, IR may be viewed as an appropriate response to increased nutrient accumulation as originally suggested by Unger (32), representing part of the cells attempt to return to an energy neutral situation. This concept potentially changes our thinking concerning therapeutic modes of treating metabolic disease."
Aside: the plural possessive of cells is correctly cells'. I merely reproduce the error in the quote, along side my own many transgressions. Grind your teeth at will. End aside.
Especially:
"representing part of the cells attempt to return to an energy neutral situation"
Insulin resistance is adaptive. Almost always.
The paper was written in 2009.
The multiple authors represent a large, two-university group, with the to ability to finance lovely, detailed laboratory work. Where did so many people get this unlikely idea that insulin resistance is an adaptive defense against oxidative stress?
Well it certainly wasn't from me, back in 2009. Nowadays, maybe.
Could it have been from Adnan Erol?
Who?
He's the chap who wrote this paper:
in Bioessays, published in 2007, two years before the above paper.
It's hard to see who might have precedence here. The amount of lab work in the 2009 paper suggests that that work may have been ongoing before Erol's 2007 paper was published, but it's hard to say. I cannot find anywhere that Erol's work is cited in the 2009 paper, but that doesn't mean they haven't read it.
So what else has Erol published? It turns out that Erol is quite a common surname in Turkey. There are 270-ish hits if you just click on the author link in Erol's PubMed abstract. These include many different christian names, or perhaps I should say "given" names, in view of the part of the world from which Dr Erol hails.
Searching on "Adnan Erol" gives 27 hits. All appear to be the same author and all, at a glance, look deeply insightful. They are all single author papers.
He thinks for himself.
I get the impression that Adnan Erol is a medically educated/qualified chap in Mansia, Turkey, with a keyboard and access to PubMed. In possession of enquiring mind.
I empathise with him.
I also disagree with him in places. His concept that insulin resistance at the whole organism level is maladaptive is one such. Also, because he (understandably) lacks the Protons hypothesis of obesity, he has to fall back on the old thrifty genome concept to explain obesity through "over eating".
But his overall basic concept, yes. Ten out of ten.
Peter
Interesting reading. Glad you’re blogging again. 😃
ReplyDeleteTa, you just have to leave social media...
DeleteErol's list of 27 publications covers an interesting range. There is a flurry of output in 2021–2022. I like this guy's thinking; a 2022 paper starts out "COVID-19 is a generally benign coronavirus disease that can spread rapidly, except for those with a group of risk factors." ("Importance of Efferocytosis in COVID-19 Mortality").
ReplyDeleteThere is nothing listed for him after 2022.
Yes, but at least he is not recorded as deceased! He does describe himself as an independent researcher. Agree!
DeleteHi Peter,
ReplyDeleteAny thoughts on ways to reduce insulin levels?
Eating fewer carbs always seems top of the list (and maybe protein, although this seems much less important), but maybe there are other things with a decent effect?
And if eating some carbs (say 50g or 100g/day) do you think it makes any difference if they're in one block or spread through the day?
Resisting insulin generally, but then being sensitive to it when required is ... confusing!
Malcolm.
I think one approach is by bypassing the insulin signalling system completely might be effective. The alternative route to utilise both glucose and FFAs is the AMPK. What is utilised thus does not require insulin... AKA exercise. Also I think protein restriction might be more important than you suggest. Protein stimulates insulin and glucagon secretion in parallel acutely. But if you eat 200g of protein and maintain acute normoglycaemia, what will happen to all of the glucose derived from gluconeogenic amino acids? Probably delayed... Do I hear insulin? I've heard suggestions that many people on long term LC do not always maintain deep ketosis. Probably yesterday's protein is maintaining low grade glucose output? After 20 years on keto-ish eating then +++ on ketostix is easy if fat is high and protein low.
DeletePardon the several typos!
Delete