http://www.sciencedaily.com/release...40825185319.htm




No time to read this myself... all I can say is, has Stephan Guyunet heard about this? I thought the research community had totally exonerated insulin.

Just in case of being misunderstood... that was sarcasm.

Thanks for posting, teaser. No criticism meant to you because we all discover the truth by different means, but if you've been reading Dr Jason Fung's blog , this is Old News.

On the other hand, confirmation of a theory is always good news and there seem to be many slow learners out there still debating whether "overproduction" of insulin is a major player in weight gain. It is good for all of us to know that the theory holds up through one more study.

Oh, Teaser. It's a mouse study. Hehe.

Is this edit correct?

...lack receptors in the liver for a hormone called glucagon...

or is the lack of receptors in many locations?

"The optimal therapy, they propose, should be diet restriction and..."

Hmm. Weird. I wonder what one should keep low to create an optimal therapy......

Not sure what you mean here... but the idea that insulin is linked to obesity was familiar to me long before Dr. Fung had a blog or any videos on Youtube. I like his stuff though. Personally I learned it from that Dr. Atkins fellow Dr. Fung keeps dissing.

Read this forum long enough, and to tell the truth, most of what Dr. Fung has to say seems like old news.

The glucagon thing is interesting. It's not the only glucose-raising hormone that contributes to obesity. Just about everybody's aware of the sort of central, visceral obesity that cortisol contributes to. And an adrenalectomy protects against obesity as well. The Eades in Protein Power spoke of glucagon's anti-insulinogenic effect. But any hormone that opposes the action of insulin--if things go down just wrong, you've got elevated blood glucose, and it takes more insulin to achieve normal blood sugars.

There are some studies with leptin, where type 1 mice that don't make any insulin do all right if you give them enough leptin. The leptin downregulates glucagon massively. It isn't really the lack of insulin as such that causes diabetic ketoacidosis and the wasting away of type I diabetes, so much as the uncontested hormonal effects of glucagon.

Martin, when it comes down the the basic functions of hormones like insulin and glucagon, I have no prejudice agaiinst mice. I also have no idea whether inappropriate glucagon signalling has anything to do with human obesity. Whether it does or not... as a low carber, the idea of reduced glucose production by the liver is appealing. An increased glucose production doesn't have to be the cause of weight gain, necessarily, for decreased glucose production--and a concomitally lower insulin--to be protective or therapeutic against it. I prefer to go with nutritional ketosis. We already have a number of nutritional approaches besides this available. Moderate alcohol. Vinegar (connection here--alcohol metabolized to acetone, vinegar is acetate, the one is the ketone form of the other). And ketone esters--unsurprising given the effect of acetate and alcohol/acetone.

I wondered if I might be misunderstood....I guess if you have to ask...

Yes, certainly insulin has been known for a long time to make you fat, and I understand that it has been known that lowering insulin levels would allow you to lose weight, but the part that reminded me of Dr Fung was the idea that the treatment for type 2 diabetes of giving insulin or medications that increase insulin production is just making the diabetes worse. That it is the insulin, not the high blood sugar per se, that is causing the diabetic symptoms such as heart disease, etc. I'd always thought it was the glycation from the high blood sugars doing the damage, have never thought about it being the insulin. That was the distinction that Fung made for me, and I saw it in that article as well.

I'm feeling a little disillusioned with Dr Fung because of his insistence that Atkins was always a high protein diet, and then yesterday he described it as low fat, low carb...WTF? Of course his protocol is better if you mis-characterize Atkins. Bernstein has been advocating lowering protein to reduce blood sugar and increase weight loss since his first book, though I've never actually seen that in any of the Atkins books (not to say it's not there, just don't remember seeing it).

I actually like Dr Fung's stuff... my reaction may have been a bit over the top. New or not, it's nice having all that information in one place. He does sort of try to take everything related to insulin into account.

I don't think I want high insulin or high glucose.

Well, true. I'd always heard diabetes described as a disease of high blood sugars but Dr Fung contradicts that saying it is a disease of high insulin levels. I know I've not read all the studies that you have, but it's the first time I'd heard it characterized that way.

Keep those studies coming....I love reading them.

I think the focus on glucagon and glucose is a mistake. In the Boston paper we discussed below, we see that BG can go extremely low yet there doesn't seem to be any detrimental effect. The idea of glucagon is it will raise BG when it gets too low. Well, if 9mg/dl is not too low, how low must BG really go for glucagon to respond?

http://forum.lowcarber.org/showthread.php?t=462193

I checked the Wiki page for glucagon and found this interesting tidbit: http://en.wikipedia.org/wiki/Glucagon_hormone_family

My paradigm says ketones are the primary regulator of all fuel substrates through their action on insulin receptors in the liver. Glucagon increases ketogenesis, therefore ketones should also act on glucagon receptors in the liver, most likely shut them down.

I also read that ketones inhibit glucagon, which is most likely why when there's tons of ketones in the blood, even if BG goes extremely low, glucagon won't respond to this.

Now let's completely shut down ketogenesis with a nice big bolus of dietary glucose, and therefore a nice big bolus of insulin. How does glucagon respond to this, if it should normally increase ketogenesis? Well, it should respond by increasing ketogenesis, and the liver now has tons of glucagon receptors open for this job, since they are not being shut down by ketones, which are now almost non-existent.

So what happens to BG at this point? It goes up. But unlike ketones, it goes up way higher than normal precisely because of the dietary bolus which adds to the total available BG. No such dietary source of ketones for this effect to occur with blood ketones. Only once excess BG is dealt with will ketogenesis resume. When there's no dietary glucose bolus, ketogenesis is not inhibited even if we eat tons of protein, because protein isn't converted into glucose, it's stimulating glucagon, which promotes glucogenesis and promotes ketogenesis, both of which to compensate for the insulin rise that comes from eating protein.

Now if we still believe glucose is absolutely required by the brain for example (which is why we focus on the effect of glucagon on blood glucose, but ignore all its other effects), consider that the blood that goes into the brain to feed it with glucose, also contains cells which can only use glucose for fuel - red blood cells - and those cells won't just hold their breath when they're in the brain's vasculature. They will continue to take in and oxidize glucose to perform their primary function of delivering oxygen to the brain, and I believe much of the glucose utilization we see when we look at the brain comes from red blood cells.

Granted, this is just how I see it, not necessarily how it actually works, but it should be enough to illustrate that focus on glucagon and glucose is a mistake.

I was going to go into this yesterday... yes. I had a study in mind where they showed different effects of adrenaline based on whether and how long a person had been fasting... the basic drive isn't for glucose itself necessarily, but for what a person gets from glucose--largely fodder for the brain's mitochondria. We can get that from ketones as well. A hormone that increases both glucose production and free fatty acids, say--in a fasting person or a person on a long-term ketogenic diet, it might serve more to raise ketones, through the increase in free fatty acids, than to raise glucose, and the ketones themselves have a tendency to decrease glucose metabolism while they're at it.

But... when we're talking the pathology of type II diabetes, we're not talking about a population that's primarily eating a low carbohydrate diet. We can agree that they should be. Within the context of a high carbohydrate diet--or just an insufficiently ketogenic low carb diet--glucagon might very well be a villain. Because if you do have replete glycogen stores in the liver--then the most powerful effect of glucagon on the metabolism is absolutely the increase in blood glucose. We're still talking carbohydrate drives insulin drives obesity--but, it's not just about dietary carbs, it's also about the habitual stores of glucose you're walking around with between meals.

I have my own theory about the "obligate" need for glucose, at least for glucose that get's "used up."

Your red blood cell theory is fine--except that the reason red blood cells need glucose is that they lack mitochondria. Instead of the more complete oxidation of glucose that happens in many cells, red blood cells break glucose down to lactic acid or pyruvic acid. During starvation, much of the gluconeogenesis is just a cycle--lactic and pyruvic acid being synthesized into glucose. This cycle doesn't require any new glucose carbon to enter the system--energy from fat metabolism is all you need to recycle that carbon.

A starving person might go through 150 grams of fat a day, resting. That's maybe 33.75 grams of glycerol released. On top of that, there's some obligate use of protein--largely to feed substrate into the krebs cycle, the bits and pieces that can't be provided by most fatty acids.

I find the "obligate" release of glycerol that a person's metabolism needs in order to survive starvation is rather close to the 24 to 30 grams that authorities say is the "obligate" glucose metabolism during starvation. What else could we do with it? Store it as glucose? Eventually, glycogen levels would rise enough to get glycolytic metabolism going again. Maybe we burn it because it has to go somewhere, and for no other reason.