Re: Researchers Discover Mechanistic Link Between High-Fat Diet and Type 2 Diabetes

Many of the posters here are falling into what one may call "the
nutritional science trap." To say "high fat" means nothing, unless you
are purposely trying to confuse or mislead people. Each fatty acid
produces different physiological effects, and other factors such as
quantity and accompanying biochemical activity/oxidative stress, will
play a role as well. "Nutritionists" do not take these factors into
account most of the time, so their conclusions are often wrong and
misleading.

The other trap is the "key protein trap." You read a report about a
researcher who says he/she found the "key" protein "responsible" for a
"disease," but the real question is "why does that protein malfunction
in some people but not others?" They will look down at the ground and
say, "well, I guess it must be the genes," which is nonsense, because
once you reach adulthood there are few "genetic diseases" that will
just happen for no reason. Some people are more susceptible to certain
kind of stressors, but without those stressors, such as a diet high in
oxidized cholesterol, there won't be genetic expression to that degree.
Scientists are generally not interested in making the link with diet,
though, because they assume the "nutritional scientists" are hard at
work on such matter, but the nutritionists are just about totally lost
in the fog of their own making, for the most part (such as the
ludicrous "essential fatty acid" claim).

Not long ago, there was a similar report on Type 2 Diabetes, and it's
one of the "I found the key protein" kinds, but then I researched the
protein and, as is almost always the case, discovered that certain
stressors are needed for its expression. So yes, some people are a bit
more susceptible genetically, but if you avoid the stressors, you
should be okay, at least until you are very old (if you are fortunate
enough to live that long anyway). Most of my posts address how to
avoid the most common stressors, especially dietary ones. Here are the
relevant papers:

9/8/2005

Key Regulator Of Blood Glucose Levels Discovered

La Jolla, CA -- In many patients with type 2 diabetes, the liver acts
like a sugar factory on overtime, churning out glucose throughout the
day, even when blood sugar levels are high. Scientists at the Salk
Institute for Biological Studies discovered a key cellular switch that
controls glucose production in liver cells.

This switch may be a potential new target for the development of highly
specific diabetes drugs that signal the liver to reduce the production
of sugar. The Salk researchers, led by Marc Montminy, a professor in
the Clayton Foundation Laboratories for Peptide Biology, published
their findings in the Sept. 7th online issue of Nature.

"It is very exciting to understand how glucose production in the liver
is regulated. Now, we can try to improve the way how type 2 diabetics
handle blood sugar," says Montminy.

The newly discovered switch, a protein named TORC2, turns on the
expression of genes necessary for glucose production in liver cells.

When describing glucose's role in health and disease, Montminy compares
the human body to a hybrid car that runs on a mix of fuels depending on
its activity status: gas, or glucose, is used for high-energy
activities, and battery power, or body fat, for low-energy activities.
During the day, when food refuels the "gas tank," the body burns mainly
glucose, and during sleep, it burns primarily fat.

The body switches from glucose to fat burning mainly in response to two
key hormones -- insulin and glucagon -- that are produced by the
pancreas. During feeding, the pancreas releases insulin, which promotes
the burning of glucose. At night, however, the pancreas releases
glucagon into the bloodstream, which signals the body to fire up the
fat burner.

But even during sleep, our brain needs a constant supply of glucose to
function properly. For that reason, our body actually manufactures
glucose during sleep or when we are fasting. That process, called
gluconeogenesis, is carried out mainly in the liver.

Insulin normally shuts down the ability of the liver to produce
glucose. In individuals with Type II diabetes, however, insulin is
unable to inhibit sugar production in the liver, "either because the
pancreas is not producing enough insulin or because insulin's signal
can't be 'heard,'" says Montminy. When the liver is unable to hear the
insulin signal, excess glucose builds up in the bloodstream.

In addition to so-called insulin sensitizing drugs that allow insulin
to work better, researchers are looking for alternative ways to shut
down the production of glucose in the liver of diabetics. "Figuring out
how to control glucose production in the liver is critical because many
complications of diabetes, such as heart disease, kidney failure and
blindness, can be reduced by maintaining a very tight control over
blood sugar levels," he says.

As glucose levels run low during fasting, the pancreas sends out the
hormone glucagon and instructs the liver to produce glucose. This
increase in glucagon turns on the TORC2 switch and allows the liver to
make more glucose. Mice that were genetically modified to make more or
less TORC2 produced more or less glucose depending on the amount of
available TORC2 (transducer of regulated CREB activity).

Most of the time, TORC2 sits in the cellular compartment that surrounds
the nucleus, where all the genes are located. When a glucagon signal
arrives, the TORC2 switch crosses the nuclear membrane, teams up with
the transcriptional activator CREB and turns on all the genes necessary
for gluconeogenesis. "Being located in a different part of the cell is
what keeps the TORC2 switch off," explains Montminy.

The researchers also discovered that a chemical modification on TORC2
itself sequesters the protein in the cytoplasm, the viscous substance
inside the cell that surrounds the nucleus. "Since we now know the
molecular mechanism by which TORC2 is inactivated we can start looking
for small molecules that do the same thing," says Montminy.

Source: www.sciencedaily.com


And here's a study about this protein:

This is the html version of the file
http://pages.unibas.ch/diss/2005/DabsB_7138.pdf.

RESPONSES TO HYPOXIA VIA mTOR
Role in Endothelial Cell Proliferation and HIF-1a Stabilization
Inauguraldissertation
zur
Erlangung der Würde eines Doktors der Philosophie
vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät
der Universität Basel
von
Weimin Li
Aus Qingdao, Volksrepublik China
Basel, April 2005
Page 2
1
Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf
Antrag
von
Prof. Michael N. Hall, Prof. Gerhard M. Christofori und Prof. Edouard
J. Battegay.
Basel, den 5. April 2005
Prof. Dr. Hans-Jakob Wirz
Dekan der Philosophisch-Naturwissenschaftlichen Fakultät

Here is a passage from this study that makes the point about stressors:

"Common triggers for mTOR signaling

The stimulatory inputs include nutrients such as amino acids, glucose
and fatty acids,
energy such as ATP, growth factors such as insulin, IGF and PDGF,
oxidative stress,
hypoxia, and DNA damage caused by chemical compounds or radiation.
As will be discussed later, mTOR positively regulate ribosome
biogenesis and mRNA
translation, the processes that require a large amount of amino acids.
The
observations that some neutral amino acids contribute to the
phosphorylation state of
S6K1 and elF-4E binding protein 1 (4E-BP1), two downstream targets of
mTOR,
provide a link between cellular demand of amino acids and mTOR
signaling."

Then there is raw demographic data. You just don't find type 2
diabetes among Asians who are on diets high in coconut products, nor
anything considered a "chronic disease" in "advanced Western nations."
Several on point studies, including ones that involved taking tissue
biopsies from the natives, have also argued this directly. I've cited
them here many times, but you can read Bruce Fife's "Saturated fat may
save your life" for a less technical presentation that included a
discussion of these studies. He wrote a book after that called
"Coconut Cures" which also has many such citatations from the
literature.

.

Relevant Pages

  • Key regulator of blood glucose levels discovered
    ... Key regulator of blood glucose levels discovered ... blood sugar levels are high. ... liver cells. ... turns on the TORC2 switch and allows the liver to make more glucose. ...
    (alt.support.diabetes)
  • Re: Can there be an afternoon liver dump?
    ... a "liver dump" (use whatever technical ... meals to become blood glucose, rather than the blood glucose being ... is less simple because the real problem may be our insulin resistance ... As diabetics, T1 or T2, there is really only ...
    (alt.support.diabetes)
  • OT : Liver Dump
    ... Here is my working definition of: Liver Dump: ... It is an unexpected and large amount of glucose dumped by the liver in the ... Is Liver Dump equivalent of Glycogenolysis ...
    (alt.support.diabetes)
  • Re: How low is too low?
    ... Or will my liver kick in and dump some sugar ... I normally take 2x500 mg Metformin at midnight; ... high from the glucose. ... liver from excessive glucose dumping and reduces the Insulin Resistance ...
    (alt.support.diabetes)
  • Re: Diseases caused by sugar poisoning (1910)
    ... > Glucose oxidation by mitochondria is much safer than fatty acid ... Since glucose doesn't enter the mitochondria you're on shakey ground ... Acetyl CoA is also made from amino acids. ...
    (sci.med.nutrition)