A New Paradigm of Insulin Resistance – T2D 13

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Our current paradigm of insulin resistance is that of a lock and key. Insulin is a hormone that acts upon a hormonal receptor on a cell surface in order to have an effect. 

This is often referred to as lock and key model. The lock is the insulin receptor which keeps the gates to the cell closed. When the proper key (insulin) is inserted, then the gate opens to let glucose from the blood inside the cell. This glucose is then able to power the cell machinery.

Once you remove the key (insulin) then the gate closes back up and glucose in the blood is no longer able to go inside the cell.

What happens during the phenomenon of insulin resistance? Classically, we imagine that the lock and key no longer fit very well. The key (insulin) is able to open the lock (receptor) but only partially and not very well. As a result, the glucose is not able to pass through the gate normally.

This results in lower than normal amounts of glucose inside the cell. The glucose, which is now blocked by the closed gate, piles up outside the cell in the blood, which we can detect as elevated blood sugar and make the clinical diagnosis of type 2 diabetes.

This has also been described as a state of internal starvation since the cell has little glucose on the inside. The knee-jerk reaction is for the body to increase production of insulin (key). Since each key works less well than previously, the body over-produces the number of keys to make sure that enough glucose goes into the cells. A nice neat theory.

The problem, really, is that this paradigm does not really fit reality. First, is the problem the insulin, or the insulin receptor? Well, it’s really quite easy these days to look at the structure of insulin and the structure of the insulin receptor of insulin resistance patients. You simply isolate the insulin or some cells and check their structure with fancy molecular tools. It immediately becomes clear that there is nothing wrong with either the insulin or the receptor. So what’s the deal?

The only remaining possibility is that there is something that is gumming up the system. Some kind of blocker that interferes with mechanism of the lock and key. But what? There’s all kinds of theories. Inflammation. Oxidative Stress. Advance glycation End Products. All the usual buzzwords that come out when doctors have really no idea. With this model, we have no real friggin’ idea what caused the insulin resistance. Without understanding what causes IR, we have no chance of treating it.

Then there’s the central paradox of hepatic insulin resistance. Let me explain. Insulin has two major actions on the liver. Remember that insulin goes up when you eat. It tells the body to stop producing glucose in the liver (gluconeogenesis) because there is lots of glucose coming in from the stomach (food). This is mediated through the FOX01 pathway.

The second major action in the liver is to increase the production of fat (De Novo Lipogeneis (DNL)). This is to deal with the incoming flood of glucose that the body can’t use right way. This is mediated through the SREBP-1c pathway.

So, if the liver becomes insulin resistant, then the effect of insulin should drop for both of these actions. That is, the liver should continue to make glucose, and stop making fat. But that’s only the case for gluconeogenesis. That is, during insulin resistance, the liver continues to make new glucose as expected. But DNL (making new fat) continues and actually increases. So insulin’s effect on DNL is not blunted but accelerated!

What the hell?

How in seven hells can this insulin resistant liver selectively be resistant to one effect of insulin yet accelerate the effect of the other? In the very same cell, in response to the very same levels of insulin, with the very same insulin receptor? That seems crazy. The same cell is insulin resistance and insulin super-sensitive at the same time!

JapaneseSubway2How can we explain this paradox?

We need a new paradigm of insulin resistance that better fits the facts. In fact, we can think of insulin resistance as an overflow phenomenon, instead of a lock and key one. All we really know about insulin resistance is that it is much more difficult to move glucose into an ‘insulin resistant’ cell than a normal one.

But this does not necessarily mean that the door is jammed. Instead, perhaps the cell is already overflowing with glucose and therefore more glucose cannot go in.

Imagine the cell to be a subway car. When the door opens, the passengers on the outside (glucose in the blood) march in a nice orderly manner into the empty subway car (cell). Normally, it doesn’t really require much of a push to get this glucose into the cell (insulin gives the push).

But during insulin resistance, the problem is not that the door does not open. The problem, instead is that the subway car (cell) is already overflowing with passengers (glucose). Now the glucose outside the cell simply can’t get in and is left crowded on the platform.

Insulin tries to push the glucose into the cell like the Japanese Subway Pushers, but they simply can’t do it because it’s full. So, it looks like the cell is resistant to the effects of the insulin, but really the problem is that the cell is already overflowing. So, the knee jerk reaction is to manufacture more insulin (pushers) to help push glucose into the cell. Which works, but only for a while.

So, the cell is not in a state of ‘internal starvation’. Instead, the cell is overflowing with glucose. Glucose starts spilling out into the blood, which looks like gluconeogenesis has not been stopped which is consistent with insulin resistance. However, the Insulin and its Receptor are fine; they are simply overwhelmed by exogenous glucose ‘toxicity’.

But what happens to fat production?

In the classic model of insulin resistance, the paradox was that DNL was enhanced, not decreased which looked a lot like heightened insulin sensitivity instead of resistance. But in the overflow model, the DNL would be enhanced because the cell is trying to rid itself of the excess glucose by producing extra fat. The cell is overflowing and not in an ‘internal starvation’ mode.

Why is this critically important? Because understanding this new paradigm will lead to the answer of how insulin resistance develops and what we can do about it. The problem does not lie with either insulin nor the insulin receptor. Both are normal. The problem is that the cell is completely stuffed full of glucose. So, what caused it? The answer then seems obvious – it’s a matter of too much glucose and too much insulin. In other words, it was the insulin itself that caused the insulin resistance. We don’t need to chase shadows looking for some mysterious cause of insulin resistance.

Once we understand that excessive glucose and excessive insulin is the cause of the insulin resistance, then we can now devise a rational treatment. Reduce insulin and reduce glucose. Once you reverse the insulin resistance, you cure the type 2 diabetes.

2017-10-19T12:31:12+00:00 86 Comments

About the Author:

Dr. Fung is a Toronto based kidney specialist, having graduated from the University of Toronto and finishing his medical specialty at the University of California, Los Angeles in 2001. He is the author of the bestsellers ‘The Obesity Code’ and ‘The Complete Guide to Fasting’. He has pioneered the use of therapeutic fasting for weight loss and type 2 diabetes reversal in his IDM clinic.

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86 Comments on "A New Paradigm of Insulin Resistance – T2D 13"

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Dirk Van Giel
Guest

This is amazing! If cells are overflowing with glucose wouldn’t it be a great idea to start exercising and make sure the glucose in these cells are burned?

Archie L. Tucker
Guest

What a novel idea; reckon the doctors will ever catch on? Fasting works even better. What if we combined the two??? “What a wonderful world this would be”.

David
Guest

Are there any actual studies of fasting+exercising?

Bethany
Guest

Krista Varady did a study that appears in the October 2013 edition of Clinical Nutrition about combining alternate day fasting with endurance exercise. She was specifically focusing on coronary heart disease risk factors, but did find that weight loss was greater in the fasting + exercise group vs. the just fasting group or just exercise group.

As we would expect, just fasting had significantly more weight loss than just exercising. Keep in mind that this was her version of alternate day fasting, which includes up to 500 calories on “fasting” day and eating whatever you want on “feast” days.

BobM
Guest
I personally would find a day of 500 calorie eating difficult. I might be able to do it if I ate breakfast with 500 calories, but I couldn’t do it with 500 calories of dinner. I’d rather either eat ad libitum (feasting, I guess–eating whatever I want) at dinner or just skip dinner altogether. I personally think exercise is useless for losing weight, unless you exercise a ton (and then I think you’re changing your insulin response, which is the real cause of weight loss). Personally, by using low carb and fasting, I’ve lost weight and at the same time,… Read more »
David
Guest

Bob,

Hard to say exercise is useless. An hour of moderate effort on the elliptical or the treadmill burns 800+ calories for a 200 lbs man. At higher intensities, or weight training for that matter, you’re likely shifting your own bodies hormones, not just insulin.

MickiSue
Guest

Great idea, if exercise didn’t tend to increase appetite, and if, on a SAD, that increased appetite didn’t trend to consuming more carbs, which then further stuff the cells…

sten bjorsell
Guest

Sounds great.
Where are the studies showing that in DB-2 /insulin resistance cells are not starving of glucose (like they do in DB-1)?
When it is clear that it is proven beyond doubt the classical method of insulin treatment of DB-2 is really dead. It
would also explain why patients get worse and die sooner with more intensive insulin treatment, the outcome of various trials, the ACCORD trial that showed increased mortality with more insulin, for instance.

David
Guest

This is a little bit against the spirit of this blog, but does anyone have an idea if it’s better to have dessert before or after the meal?

Steve
Guest

This is answered within the spirit of this blog –

You should only eat dessert after the meal. You should also skip the meal. 🙂

BobM
Guest

I’ve been thinking it’s better to have dessert earlier in the day, then find a way to walk it off. For instance, we’re going on vacation soon and will likely have ice cream with the kids. We used to always have ice cream after dinner, but I’m thinking we should have it perhaps after lunch, then go do something (go hiking, walk on the beach, etc.) to use up the excess glucose. And, of course, fasting after returning from vacation works well too.

Walt
Guest

It all hinges on what you mean by dessert. If it involves sugar and floury baked goods then the answer is NO DESSERT FOR YOU.

David
Guest

Never having another dessert is unlikely and impractical as a suggestion.

jim
Guest

I started having recognizable symptoms of alzheimer. Going keto with zero carbohydrates became much easier and very practical.

Karen
Guest

He didn’t say no dessert he said no sugar laden dessert. I think a lifetime without such things is easy if it means you solve your health issues

Katie
Guest

I have dessert A LOT. I’m just saying.

Cole
Guest
Mary
Guest
Though I love Steve’s reply, I also remembered another blog that might actually have an answer at least by logical extension: https://intensivedietarymanagement.com/circadian-rhytms-fasting-17/ For instance: “Now, this does not necessarily mean that you must eat a large meal as soon as you wake up. But it means that perhaps eating a large meal in the evening (after the sun goes down) may cause a much larger rise in insulin than eating that same meal during daylight hours.” Since reading that I have made decisions not to eat (former type II off meds for a year now after 6 months intermittent fasting… Read more »
Archie L. Tucker
Guest
Wow! I’ve studied this for years. I’ve taught my students about the lock and key model and this seems to be such a better understanding. I’ve been reading your work and watching your videos since I stumbled across it on the internet. I used to think I was studying diabetes for my brother who has suffered with it for years. Then, long story short, I found out I had it. I cured myself by eliminating all foods that quickly turn to sugar. I have noticed over the years that when I eliminate sugar, my triglycerides fall precipitately. So, the old… Read more »
Carol Kushner
Guest
My diabetes Type II is also cured using intermittant fasting and for the”eating days” I use the recipes on diet doctor.com. I take no medication for diabetes and I have stopped taking my statin — my only prescription now is for a blood thinner (Apixaban) and I also take Vitamin D. I still have weight to lose so I will continue with this regime until I’ve lost the excess weight and then I will be one happy girl!! My blood sugars have been perfectly normal for three weeks without diabetes meds (gliclazide — I never took insulin). This is a… Read more »
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Michael
Guest

Interesting theory. One thing that it doesn’t explain though is the fact that many T2D:s on LCHF still need some medication. Why is that If there is no structural problem with their insuline receptors?

Alan
Guest
You can be LCHF and still have high-enough insulin levels. Protein has about half the insulin-raising effect of carbs, so if you eat enough protein you raise insulin. If you’re already insulin resistant it may not take too much of a rise in insulin to prevent your fat cells from releasing energy. LCHF does not recommend as much fat as a ketogenic diet, which for clinical treatment purposes is about 90% calories from fat. Basically, have a little salad and bacon bits with your glass of olive oil. (Okay, 300 calories of spinach is a boat-load of spinach). When I… Read more »
Nancy J
Guest

Could there be a different mechanism for liver cells vs. peripheral cells, or do you think one mechanism can explain both?

Ari
Guest

This is a great explanation! When cells get crammed with glucose for a long time, what happens? Fermentation starts. You got cancer! This fits so well to everything else, it must be right. What an astonishing logic you have, Dr Fung!

Joan Day
Guest
Dr Fung–you are just fabulous–you can explain things so well. I love the example of the subway train–many of your followers as you know are not PHD.s , scientist/researchers, or Drs. –we the “common people” , patients, and internet fans, so enjoy your blog, and words of wisdom, that we can understand. [because of the way you explain things.] You are an amazing teacher, and healer. You have helped so many people, you may never really know how many–I for one, will be forever grateful. I found you after an article in the Toronto Star, near the end of January… Read more »
rick mccarthy
Guest

Great post. Dr. Fung’s the best. I’m enjoying the heck out his book. Thanks Doctor.

Samuel
Guest

Reaction rates very much depend on the concentration of the reactants. If you get too much product, then things slow down or even reverse. This is all basic physical chemistry and I wonder if there is a lot of research going on to study the chemical pathways in detail and determine where the backups are occurring. It certainly would provide a basis for your theoretical explanation, and would be a lot more satisfying than the lock and key model.

Diana
Guest

Okay then if I have so much stored sugar in my cells why can’t it be used properly for energy? Why the lethargy? I have believed it was because the sugar couldn’t ‘get in’ Now I am confused again…

Martin
Guest

Think of molasses or honey inside your cells…

Diana
Guest

Good analogy Martin

Sonja
Guest

Diana- Sonja here. I totally agree with you. pls scan down ~10, and see what I wrote! something more is going on.

Alan
Guest
Check out Wikipedia for “autophagy”. Autophagy is a natural process where damaged and tired proteins and organelles inside your cells are broken down and recycled for parts. When insulin and amino acid levels are high enough they inhibit autophagy. It’s like never taking the trash out of your house even while you’re regularly buying groceries. As things pile up inside the cell they get in the way of other healthy cell functions. We need to stop eating proteins and carbs for a period of time in order to allow autophagy to occur. (It’s my understanding that eating fat will not… Read more »
BobM
Guest

Is there any way to develop a test or study that could prove this hypothesis correct and the original hypothesis wrong? Sort of like swallowing bacteria and getting an ulcer to prove that (some) ulcers are caused by bacteria?

Zig Euner
Guest
1) It’s still a form of “internal starvation”, though. If hepatic cells are chugging along conducting DNL, then that glucose is not being used for energy. And if they’re doing DNL, then they’re also not doing beta oxidation. So hepatic cells are using glucose for DNL, and not burning it for ATP, and also not burning fats. So they’re experiencing ATP starvation, and the rest of the body that relies on hepatic cells to provide energy substrates will also experience a degree of ATP starvation. So the hepatocytes engage in gluconeogenesis, because they’re getting the ATP starvation signal. What a… Read more »
Tom
Guest

Zig, thanks in particular for comment #1. I was specifically trying to work out the “internal starvation” aspect in my own mind. This is quite helpfull.

erdoke
Guest
I’m afraid in this case you are completely off. The reason why there seems to be a controversy in “selective hepatic insulin resistance” is because of focusing on only the liver. Metabolism is coordinated by an adipose-liver axis with regular modulation by the immune system. If something appears controversial in the liver, then the most likely explanation is that something else is happening in the adipose tissue. The whole “glucose needs insulin to enter cells” is a medical fallacy which has nothing to do with basic science. Yes, in hyperglycemic and hyperinsulinemic conditions (i.e. in disease) something like that happens,… Read more »
12Kevin
Guest

Regardless of the inherent limits of explicating complex interdependent functions, would you agree that nutrition systems (like periodic fasting) which lower insulin levels remain sound approaches to modern metabolic diseases? And/or, that tracking insulin levels is a good proxy for predicting current and future metabolic health?

erdoke
Guest

@12Kevin
Yes, maintaining adipose insulin sensitivity for feeding and their physiologic insulin resistance for fasting is crucial. Both a low insulin load diet and fasting help. No major disagreement in that part.

Martin
Guest
“Insulin’s single most important role in the body is to suppress lipolysis” This may be true, but because insulin first mission is to get rid ASAP of the excess of glucose in the bloodstream…because excess glucose is toxic. (so better the cells quit using fatty acids and start burning sugar NOW!!!) “Whenever acetyl-CoA is low, GNG slows down.” When GNG is activated (glucagon/insulin ratio), oxalacetate is diverted to glucose production. That results in an accumulation of Acetyl-CoA which drives ketone bodies synthesis. So when Acetyl-CoA is high may be because the Krebs cycle is lacking oxalacetate. So, “Whenever acetyl-CoA is… Read more »
erdoke
Guest
@Martin It is the role of a healthy adipose tissue to remove excess glucose from the bloodstream. It is done without much intervention by insulin. As we all (should) know by now, diabetes is not really about glucose take up, but rather disregulated hepatic glucose production (HGP). Above linked studies played a major role in our understanding how HGP goes wrong, and it happens in adipose tissue. Adipose insulin resistance when feeding is really bad. GNG is running continuously, there is no such thing as “not necessary”. The rate varies by a great extent, and Ac-CoA availability (determined mainly by… Read more »
Tom
Guest
Thanks Doc! This article offers a new paradigm which potentially clarifies so much for me. Since my diagnosis of T2D in 2008, I’ve been an avid researcher on the subject. My own research took me naturally into a Paleo type diet of my own devising. About a year later, I discovered Robb Wolf and numerous others in the ancestral/LCHF health movement, which really helped me to dial things in and leverage that knowledge in my own research and self-experimentation. About two weeks ago, I discovered your interview on Robb Wolf’s pod cast. I’ve been ravenously consuming all of your articles… Read more »
Sheri
Guest

I hope Dr. Fung does an indepth study on statins since I know first hand that my husband’s glucose bloodwork was fine but one year on statin (lipitor) his glucose was 116-prediabetic. I’m tired of a cardiologist just wanting to treat one problem but has no regard that his prescription is creating another life threatening illness. Hmmm, lower cholesterol or give a patient diabetes??? Watch “Sunday Housecalls” on Fox cable and see Dr. Samadi’s response!! I agree with his advice. I hope Dr. Fung addresses this issue head-on. Specifically about statins and diabetes. Thank you !

sten bjorsell
Guest

You do not need indepth studies ! Just google: pfizer sued lipitor causing diabetes 2, and you find that 1000’s of people are in the same seat as your HB. Please also show prints of the articles to your cardiology geniuses, as many of them rarely get new information from others than statin/meds salesmen. The problem for Pfizer is that they knew this long before they later had to warn people about it. The serious crime is in knowing to cause harm and pushing on with sales saying nothing.

Sheri
Guest

Thanks!

Amy
Guest

I love this analogy! It makes much more sense than the lock and key idea. I’ve been on the metro in Moscow, Russia. There were no pushers that I recall, but one day, during rush hour, we were packed in so tight that I was lifted off the floor part of the time. To think I’ve done this to my cells…it’s no wonder sometimes I hurt for no apparent reason!

Sonja M Discher
Guest
I just CAN’T agree with this idea that the cell is overloaded with glucose! I have forever noted that for years I have NO energy! by this new idea, I SHOULD have excess energy! But let me tell you , THAT is NEVER true. before I had the diagnosis I always complained that it seemed like I just could not get any energy into my muscles, and I was a dancer, cheerleader and weighed 102# !! . IF the cells had so much glucose, you’d think a diabetic would be CRAZY with ENERGY. THAT is NEVER TRUE!! anyother DiABETICS agree… Read more »
Diana
Guest

I have no energy either! Been that way for years. Back when I was 30, my 80-year old grandma had more energy than I had! … However when I fast my energy goes up. I am not obese but I am insulin resistant.

Amy
Guest

Could it be related to excess glucose induced inflammation? I agree that on high carb (more energy) I felt lousy. There are lots of articles out there that explain how bad oils and sugar cause inflammation. Just thinking “out loud”…

Amy
Guest

I don’t know how to put a link in right here but paleo leap has a great article about inflammation posted today…

Alan
Guest

If part of your cell making energy involved moving material from one side of the cell to the other, how well would it be able to move that material if it was packed in tight? If you made energy by walking from one end of the subway car to the other, and the amount of energy you created was determined by how fast you moved, how fast would you be able to move if the subway car was so full they needed “pushers” to get you into the car?

Burgundy
Guest
Sonja; I’ve been pondering this too. I’m beginning to think the problem gumming up the works is oxygen deprivation. Lack of cellular oxygen is possibly slowing down the metabolism mechanism and causing the backup of glucose into the bloodstream. T2Ds breath more than normal and also have more acidic urine, possibly due to low cellular oxygen levels? Hyperventilating (breathing too much) causes less oxygen to enter the cell (due to the Bohr effect), maybe we diabetics also have an oxygen resistance problem where the cell membrane is inefficient at allowing the transport of oxygen into the cell? Maybe fasting also… Read more »
alan
Guest

Anecdotally: my wife has a pulse oximeter. On a normal diet I am around 93-94 on oxygen saturation. While low carb of fasting I am at 98%. I also notice myself breathing slower and more shallow.

kirsty
Guest

Makes sense, thanks. However one question – if the cell is not in a state of ‘internal starvation’ why do those with IR get hungry? Thanks in advance!

Diana
Guest

Martin (above comment) says it’s like having molasses in our cells. That could make sense.

Diana
Guest

Oops this reply was to Sonya’s comment. Sorry.

Frank
Guest
It’s a sad state how medicine is more religious fanaticism than following the science. My cousin is T2 diabetic and her fasting glucose numbers were off the charts. I read almost every article here by that time and so I told her to switch her diet to LCHF and to intermittently fast. She has and her glucose numbers started to plummet from the first day. She’s also losing weight which I care little about but she is ecstatic about. She is so excited because she’s stopped taking her Metformin and yet her numbers are still low. She saw the doctor… Read more »
Jim M.
Guest

Wow that is just criminal!
Hope she stays strong, and finds a new doctor!

Jim MacK

stephane
Guest
So with that theory, cells would be crowded with glucose and the body would be still asking for more. But what in the first place is stuffing the cells with glucose they can’t process ? Why T2D patients report feeling lousy with no energy while their cells are full of fuel ? What if it were the mitochondrion machinery that is impaired ? What if the glucose to ATP conversion rate were poor, leading to ATP starvation which in turn drives fuel demand ? At the same time, the cells are not able to process fat because 1 – They… Read more »
Jin
Guest
I was thinking along the same lines as you stephane. My own layman theory is flour fortification poisoning. France despite consuming 40% more flour than USA or UK has less obesity, diabetes. The only difference in the flour is it’s not fortified with iron and vitamins. Good luck finding gluten free foods in France as there is very little demand for it. Many diets tell us to omit wheat and very often people feel a lot better for doing so. The last time fortification was increased coincides with huge increases in obesity and diabetes which was in the early eighties.… Read more »
alan
Guest

France also eats a lot more fat. Frois guas and cheese. Also their portions appear comically small to us Americans. Are there a lot of fat-free productd in France?

seebrina
Guest

Don’t forget too that here in the US they have added Bromine to flour and bread products which is toxic and clogs the hormone receptors. Which translates to iodine receptors being clogged coupled with no iodine in the diet any longer. Iodine is used by every cell and hormone receptors. They should outlaw this as other countries have done . I think its a multi-layered problem along with insulin resistance.

Martin
Guest

“What if it were the mitochondrion machinery that is impaired ?
What if the glucose to ATP conversion rate were poor, leading to ATP starvation which in turn drives fuel demand ?”
I think those are very interesting questions!
If glucose to ATP conversion were poor, it may be because it was not going all the way in the Krebs cycle (to CO2 and H2O(36 ATP)), but only to pyruvate and lactate(6-8ATP?)as it is when anaerobic work is done…
That will give mitochondrion less work to do, wich will bring down her machinery capacity…
Just a thought…

Sue
Guest

Another EXCELLENT Blog…. I look forward to them like a kid at Christmas and am never disappointed! This is a bit off topic but has anyone had an increase or decrease in kidney stones on a LCHF diet. Just curious.

JochyD
Guest
Dr. Fung, I just finished reading your book and allow me to “thank you” for taking your time for spreading wisdom and hope to all of us that are seeking a common sense approach to control or reverse T2D. Also, thanks to the readers, whose shares their personal story and make positive contributions to this forum. Briefly, my personal account. I am 57 and 5 feet, 9 inches tall. Last November, I ended in the local hospital due to an acute case of blurred vision, serious dehydration, and few others ailments. The lab results confirmed my suspicion. Glucose: 433, A1C:11,… Read more »
David
Guest

Congratulations Jochy, that’s a great story, you’ve dropped 34 lbs in 8 months if I’m following your timeline correctly, a steady rate of approximately ~1 lbs per week, and you’ve gone from size 40 to size 34 pants.

Have you enjoyed changing your entire wardrobe? Somebody should work out, for fun, how the amount of food money saved by fasting compares to the amount of money spent on new pairs of pants 🙂

Sue
Guest

Good one David! LOL And congrats Jochy! My husband and I have done the same thing…. slow and steady wins the race.

Eli
Guest

Amazing JochyD. Good for you!

Jona
Guest

I’ll right away snatch your rss as I can not to find your
email subscription link or e-newsletter service.
Do you’ve any? Please let me know so that I may subscribe.
Thanks.

Meg
Guest
My understanding of this paradox is that you can’t think of the liver in isolation. Most cells, including fat cells and muscle cells (but NOT liver cells) require insulin to allow glucose to come inside the cell from the blood. When they become insulin resistant, they don’t take in their share of glucose, and blood glucose remains high, while the insulin resistant cells have low internal level of glucose. The “internal starvation”, which makes you hungry, in occurring in your non-liver cells. The high blood glucose flows into liver cells, which don’t require insulin for influx of glucose. The effect… Read more »
Burgundy
Guest
So, a bit of overly simplified conjecture: a) insulin resistance is a red herring and doesn’t really exist; b) fatty acid metabolic pathway is stuck open at the cellular level, blocking conversion of glucose into ATP and using fatty acid synthesis instead; c) glucose backs-up into the bloodstream and causes insulin to go nuts and shoves it all into adipose tissue everywhere; d) fatty acid synthesis uses more oxygen without creating carbon dioxide creating oxygen starvation via the Bohr Effect and causing hyperventilation; e) fatty acid synthesis acidifies the body via lactic acid production and the low PH causes expulsion… Read more »
Barry W. |Justice
Guest

Thank you Dr. Fung, for thinking! Few practitioners go beyond the readily accepted “studies” that have traditionally become the benchmark for our lack of success in the fight against diabetes, cancer and most other health issues. In a brain dead society where early diagnosis and drug treatments are trumpeted as successes you stand out as an example of how our thoughts and beliefs can transform us into sheep or elevate us! Thank you from the bottom of my heart for making the difference for the resistance! You have become the transformer.

Barry W. |Justice
Guest

Should read in the last sentence……….you have become the elevating force!

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[…] why does this happen? The cells are already over-filled with glucose (see previous post – A New Paradigm, and Insulin Resistance is Good?). Like trying to blow air into an over-inflated balloon, it simply […]

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[…] why does this happen? The cells are already over-filled with glucose (see previous post – A New Paradigm, and Insulin Resistance is Good?). Like trying to blow air into an over-inflated balloon, it simply […]

tomer
Guest
“So, if the liver becomes insulin resistant, then the effect of insulin should drop for both of these actions. That is, the liver should continue to make glucose, and stop making fat” The two effects work in the opposite direction. The part of the GNG is true, the liver makes more fat because he thinks thats the insulin low but the liver should not stop making fat because low inuslin increase DNL. The liver feels low insulin and makes more fat, thats make sense. If the theory of the overflow is true go ahead and measure it. Meanwhile I believe… Read more »
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[…] need to understand the new paradigm of insulin resistance to understand how insulin resistance, obesity, fatty liver, and fatty pancreas are actually all […]

Marcelo
Guest

Ótima matéria, por isso que uma alimentação lowcarb é ideal pra pessoas que estão com esse problema, pois basta retirar o causador do problema

Craig
Guest

Dr. Fung,

I wonder if you are familiar with the paper linked below. It challenges the idea that insulin resistance is the primary driver of type 2 diabetes, and makes a case for beta cell dysfunction being the primary problem. Any thoughts?

http://www.medicographia.com/2011/07/%CE%B2-cell-dysfunction-vs-insulin-resistance-in-type-2-diabetes-the-eternal-chicken-and-egg-question/

Kenneth
Guest
Being a T2D since 2012, I have been under the assumption that my beta cells have diminished in productivity either by death or by dysfunction and, as such, cannot keep up with the demand I place upon my body with the foods I eat. As time progresses I have to inject more insulin unless I keep my food intake in moderation. I found that intermittent fasting has improved my body function and glucose regulation, but only if I maintain this fasting protocol. Any food intake increases my blood glucose. I take insulin and the glucose goes down. My thoughts are… Read more »
Jay remi xax
Guest
So I’m an MD and it took a second to understand this, but the root of the problem is hyperglycemia which is growing from the liver. -in order for cells to be overflowing with glucose there must be too much glucose in the cell which correctly tears down the lock and key model–in that instance the cells wouldn’t be full of glucose. – so why is there too much glucose in the bloodstream? It’s obviously not because the the glucose can’t get into the cells, because as you put it the cells are full. -therefore, it must be that the… Read more »
Matthew C. Wilson
Guest
I don’t see how this new paradigm can support the discussion elsewhere that conceives of insulin resistance as time-dependent. If insulin resistance is an “overflow phenomenon,” i.e., “Insulin tries to push the glucose into the cell like the Japanese Subway Pushers, but they simply can’t do it because it’s full,” then how could resistance get worse over time? Once the cells are full, they don’t become even fuller. Instead, they cause overflow. Actually, if you think about it carefully, the new (overflow) paradigm more of less does away with the concept of resistance per se, replacing it with fullness and… Read more »
Anna Dt
Guest
I have to admit that it took a while to grasp this but it does make sense (I have insulin resistance and read a lot about it but I have no prior scientific knowledge). However, it does bring up some questions especially regarding diet sodas and all artificial sweeteners and their impacts. I read that when you drink diet soda for instance, your brain thinks it’s real sugar and sends a message to the body to produce insulin…. What happens with that insulin according to this paradigm? Does it keep pushing all the real glucose it finds into the cell?… Read more »
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