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Interesting study about ketones and carbohydrate metabolism

Discussion in 'Fitness, Exercise and Sport' started by LittleGreyCat, Aug 31, 2021.

  1. LittleGreyCat

    LittleGreyCat Type 2 · Well-Known Member

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    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2129159/

    I can't vouch for the accuracy of this, but it does have some (at least mildly) mind boggling statement.

    Try for size:
    "Contrary to popular belief supported by the leading physiology and biochemistry textbooks, there is sufficient population of glucose transporters in all cell membranes at all times to ensure enough glucose uptake to satisfy the cell's respiration, even in the absence of insulin [21]. Insulin can and does increase the number of these transporters in some cells but glucose uptake is never truly insulin dependent. Even under conditions of extreme ketoacidosis there is no significant membrane barrier to glucose uptake – the block occurs "lower down" in the metabolic pathway where the excess of ketones competitively blocks the metabolites of glucose entering the citric acid cycle. Thus, insulin is not needed for glucose uptake and utilization in man [21]. In fact, the process appears to be general for all polar (water-soluble) substrates, as transporters are the mechanism by which they are transported across the highly non-polar (lipid) cell membranes. When insulin is administered to people with diabetes who are fasting, blood glucose concentrations falls. It is generally assumed that this is because insulin increases glucose uptake into tissues. However, this is not the case and is just another metabolic legend arising from in vitro rat data. It has been shown that insulin at concentrations that are within the normal physiological range lowers blood glucose through inhibiting hepatic glucose production"
     
  2. Oldvatr

    Oldvatr Type 2 · Expert

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    The author is a correspondent for the Journal of Sports Nutrition. The author's synopsis has no qualifications declared. There seem to be no references to any other contributors, so this is a journalist doing a trawl of published papers. Looking through the reference list at the end, the same names and institutions occur frequently, and most of them seem to be not from academic institutions but from sports nutrition sources. I have that feeling that comes when I read bad science.
     
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  3. bulkbiker

    bulkbiker Type 2 · Oracle

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    Or maybe not...

    https://academic.oup.com/ajcn/article/83/6/1442/4633149
     
  4. Oldvatr

    Oldvatr Type 2 · Expert

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    I too found this to be confusing. There are currently 14 Glucose Transporters that control the flow of glucose through the body. Most of these 'valves' are controlled by enzymes other than insulin, and, indeed, do not require insulin to transfer glucose into or out of cells. The insulin-dependant one is GLUT4 and this opens to allow glucose to pass into the citric cycle. Most of the others pass glucose, for instance through the mucous membrane of the gut to allow transport of digested glucose into the blood. There is also a GLUT required to allow glucose to pass into the red blood cells. Other cells such as sensors and the salivary glands work to detect glucose presence or absence and the result is a trigger say of amylase in the mouth, or controlling liver dump/liver fill. None of these secondary functions require insulin, But the Citric cycle is primarily tied to insulin but becomes a ketone burner in the absence of insulin. Brain cells do not require insulin, neither do nerve cells.

    At one point the author seems to be talking about transfer across the lipid cell wall and into the red blood cells, which is how we get the HbA1c This is the GLUT1 transporter and does not need insulin.

    The burning of glucose for energy is described by the Citric (or Krebs) Cycle, and the burning of fat is described by the Randle Cycle.
     
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    #4 Oldvatr, Aug 31, 2021 at 7:59 PM
    Last edited: Aug 31, 2021
  5. Oldvatr

    Oldvatr Type 2 · Expert

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    Not sure who the author of the letter is. It seems to be the author of the original paper, but he is cross-referencing to this own papers, which is not sanitary. Again, his author description has him asa a journalist, and provides no academic data. But I believe he holds an MHS which is a Master of Health Science. He has published many papers, including one on whether mechanically deboned turkey meat is beneficial to people. He also wrote on whether protein in the diet is harmful to kidneys. He does seem to be scientific based. I note that there are strong connectionsd to Messrs Lustig, Feineman, Taube et al, and surprisingly with Bernstein. So I will reserve judgement.
     
  6. bulkbiker

    bulkbiker Type 2 · Oracle

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    Fair enough.. they do seem to have about 30 entries in google scholar..and have been published in various journals so maybe not "just" a journalist..
    https://www.researchgate.net/scientific-contributions/Anssi-H-Manninen-13957755
     
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  7. Oldvatr

    Oldvatr Type 2 · Expert

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    Yes, he has' been prolific in the publications department, but I am curious as to why the author's information just refers to a press association, and the sports nutrition journal. Even the MHS citation does not refer to the adjudicating body that awarded it. I have seen a minor reference to UCFS but no accreditation to any academic establishment.

    The papers he is associated with (as author) are all review-type reports. He does not appear to do basic research himself, merely collates other people's efforts, just as a journalist does. He does not seem to query anything What makes him different from any blogger? Where does his authority lie, except in the science he plagiarises from the other papers he reviews. Is that data secure and valid?
    Or is he cherry-picking? I am curious to know. Without doing the review of every paper he references by myself, I cannot accept what he has written as being correct. Just because he echoes other claims I have read, and I happen to broadly agree with him. does not make it truth to be taken on board without question. I react this way to all papers presented here, regardless of what clique the author represents.

    For someone so active in this field, he keeps his identity well hidden. If anyone can shed light onto his credentials, then I would be interested. The researchgate info does show he is connected to PCAS Finland Oy, which is a chemical supplier to the pharmaceutical industry. It does not seem to show any other data on him.
     
  8. LaoDan

    LaoDan Type 2 · Well-Known Member

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    I did some research regarding GLUT4 and skeletal muscle. Where GLUT4 is unregulated during muscle contraction. Apparently insulin isn’t required during times of skeletal muscle stress. Not sure how that affects T2s and insulin resistance..

    My takeaway was that building muscle mass was what I needed to do to correct my situation. Increase blood flow, vascular remodeling, assisting in lymph transport.

    hope I’m right, I usually just read the abstract and conclusion, my eyes glaze over if I did into it lol
     
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  9. Oldvatr

    Oldvatr Type 2 · Expert

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    https://www.ncbi.nlm.nih.gov/books/NBK537322/
    Some bedtime reading? See Non Insulin Mediated Stimulation section.
     
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  10. Oldvatr

    Oldvatr Type 2 · Expert

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    According to Bodybuilder.com,
    "Anssi Manninen is a Finnish exercise physiologist specialising in sports nutrition and ergogenic aids and has consulted elite athletes in all sports. Anssi holds a MHS in sports medicine from University of Kuopio Medical School."

    And according to Linkedin
    "Director of Research & Development and the Chairman of the Board at Dominus Nutrition Oy & Executive Director at MBM Research Group (a not-for-profit organization)"
     
  11. NicoleC1971

    NicoleC1971 Type 1 · Well-Known Member

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    Insulin is not Needed for Glucose Uptake and Utilization in Humans

    Interestingly for me as a type 1 the reason I need insulin even without consumption of glucose is that my body's glucagon production is disinhibited in the absence of indogenous insulin. So type 1 isn't so much an absence of insulin but more an excess of glucagon leading to gluconeogenesis. The external insulin doesn't stop the gluconeogenesis but does deal with the results
    I am surprised that non diabetics don't also have a small quantity of insulin because your own insulin does inhibit gng before you even get to the production of ketones that may compete with glucose as a fuel source for the cells.
     
  12. Oldvatr

    Oldvatr Type 2 · Expert

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    This article seems to refute the linked paper in the OP and may also be of interest here.
    https://pubmed.ncbi.nlm.nih.gov/749914/


    Edit to add: This article seems to be relevant too
    https://www.yourhormones.info/hormones/glucagon/
     
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    #12 Oldvatr, Sep 1, 2021 at 1:57 PM
    Last edited: Sep 1, 2021
  13. Oldvatr

    Oldvatr Type 2 · Expert

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    I have one problem with the linked article in the OP. Its Reference[21] which he uses as evidence to support the claim that insulin is not required for glucose uptake is actually a report looking into sport use of Growth Hormone, and finding ways to detect this drug abuse in athletes. Now it is true that GH does affect the secretion of glucagon in the liver (it inhibits it when present so as to increase protein growth, which is its function).

    I have seen another paper that uses lab rats to prove this, and that paper starts with the claim that glucose uptake does not use insulin. I am not convinced that either paper offers sufficient proof to be held up as a valid contender to the established theme of the Krebs and Randle cycles as taught in the endocrinology textbooks.

    Note Glucagon not only assists glucose uptake but it is also used for ketosis and ketone generation. and catabolization. In other words, glucagon being detected just means the blood glucose level is low or very low. It is in effect the fat-adapted switch.

    If this claim regarding not requiring insulin was significant then T1D would survive longer without injecting insulin. The articles I have seen in this respect show that DKA normally requires meals to trigger it and that low carb can be effective in delaying DKA onset.
    https://www.healthline.com/diabetesmine/ask-dmine-lifespan-sans-insulin

    It seems this claim comes from a single source P H Sonkson, who appears to be a sports health physician. Edit to add: He is indeed an endocrinologist, He was a Professor, and specialized in diabetes, moving on to Growth Hormone research. After his skiing accident, he had to change course and is now working in the field of detecting drug abuse in sports up to the Olympics level. I must read his papers again in that light.
     
    #13 Oldvatr, Sep 1, 2021 at 11:38 PM
    Last edited: Sep 2, 2021
  14. LaoDan

    LaoDan Type 2 · Well-Known Member

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    Tangent, I’ve been reading about skeletal muscle transporters. All of the bodybuilding literature says to pound down carbs post workout to create an insulin response that drives nutrients into muscle cells. But it seems this might not be entirely correct. From my understanding there’s multiple transport systems.

    GLUT for glucose
    FAT, well for fat
    LAT , transports amino acids.

    Both FAT and GLUT can be activated by insulin OR contraction. I couldn’t find if LAT requires insulin.

    I wonder if my pre workout meal should be “loaded” , the one I should focus on, for maximum absorption.

    don’t mind me lol
     
  15. Oldvatr

    Oldvatr Type 2 · Expert

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    If what I read about Peter Sonksen is correct, then he deserves my utmost respect. His achievements in the field of diabetes care are impressive, and most of us probably benefit from his work in the past.
    https://www.endocrinology.org/media/1278/107.pdf

    Still not sure if turning the insulin story on its head is valid, though. Like LC diets, it flies in the face of conventional thinking and I need to climb a steep learning curve to understand the GLUT transporters in more detail.

    Is it time to ditch both the Krebs (Citric) Cycle and the Randle Cycle? That is basically what he seems to be postulating now.
    Addendum. Apparently, he was awarded the OBE
    https://www.lawinsport.com/item/peter-sonksen-obe
     
    #15 Oldvatr, Sep 2, 2021 at 10:27 AM
    Last edited: Sep 2, 2021
  16. Mr_Pot

    Mr_Pot Type 2 · Well-Known Member

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    Apparently it is all to do with overstuffed suitcases and pushing people into Japanese trains, quite simple really.
     
  17. Oldvatr

    Oldvatr Type 2 · Expert

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    This study seems to be of relevance here. It is an extract from the book "Metabolic Acidosis" and I enclose a link to Google Book Review of the relevant pages
    The published paper itself is held in the Wiley archive and copies are by request only to the authors.

    There is an interesting discussion at the end of the review that discusses T1D acidosis and is where Sonksen makes his claim, but the discussion does not seem to address this in detail or come to any agreement.
    https://books.google.co.uk/books?hl...d Diabetes and the Effects of Insulin&f=false
     
  18. Oldvatr

    Oldvatr Type 2 · Expert

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    Here is the old fashioned way of describing the use of insulin and glucagon
    http://www.columbia.edu/cu/biology/courses/c2006/lectures11/lect16.11.html

    Note that it acknowledges that insulin is not required for muscle uptake of glucose, except when resting. The muscle tissue also uses ephedrine ( aka adrenaline) to provide flight or fight energy while working or exercise.

    The other thing I found in the Sonken paper above is that it verifies the Randle Cycle in that given high amounts of both glucose and ketones, the preferred fuel is ketones and not glucose. I note that Randle is one of the participants in the discussion at the end.
     
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  19. LittleGreyCat

    LittleGreyCat Type 2 · Well-Known Member

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    Thanks - that answers one of my current questions about use of glucose when keto adapted.
    Edit: deleted because wrong way round.
    If you are running on ketones then adding glucose (through carbohydrates or by a liver dump) will not result in the glucose being immediately burned off.
     
  20. LaoDan

    LaoDan Type 2 · Well-Known Member

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    I wonder if the preferred path would then be to glycogen storage? If you’re deep in ketosis, then I would bet glycogen storage tanks have room to spare. Of course there’s some tissues that may have a preferred fuel
     
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