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Mayklub
February 20th 06, 06:44 PM
Chronic Hypoxia of Islet cell results in Diabetes Mellitus
The terms of Insulin Resistance/Sensibility should be stopped in use
C. T. Zhu
Abstract:
Etiology of Diabetes mellitus lies in unhealthy habit of dieting and
living style, which is very likely to deteriorate the hemorheology.
When the hemorheology of blood gets worse the blood would be hard to
deliver sufficient oxygen to tissue cells around body. Subsequently
tissues fall in oxygen debt and the cells couldn't generate enough
energy to meet their biological demand for energy. Body is surly to
take reaction, and there are 3 options: 1) to supply more oxygen to
tissues; 2) supply more glucagons to put more fuel into blood; 3)
increase the secretion of insulin to help cells absorb more fuel in. At
the beginning phase of progression to DM, both glucagons and insulin
are in the high altitude. When the power of both glucagons and insulin
keep in balance the sugar level of blood will be in normal at the
expense of high level of insulin, so-called insulin resistance. Sugar
glycates red blood cell (RBC) to make it loose electrical polarity, as
a result RBC aggregates. In other words, hypoxia elicits high level of
blood sugar, and high sugar level in turn promotes hypoxia of tissues.
When this relation keeps on glucagons are to override insulin and push
the sugar level higher and higher, totally out of control.
However, not all worsened hemorheology results in DM, like hypertension
or/and thrombus. This could be explained by the mechanism of secretion
of insulin, which is dictated by the rate of lactate effluent from
islet cell , and glucagons.
Background: The research to DM now is so deeply sophisticated that
ordinary one has no courage to get in it. Ironically though, the
current research could do no more than admitting that DM is incurable.
Should we suspect that current research is somewhat deviated from the
proper path? Modern medical about DM is unexceptionally based on the
two concepts: Insulin Resistance (IR) and Insulin Sensibility (IS).
When anything is good to lowering of sugar level it is read as
"increase of IS" while otherwise as "increase of IR". As IR and
IS could explain everything that results in increase or decrease of
glucose level people are complacent enough not to get into anything
behind IR and IS. This me reminds of "ghost" which was used for
quite a long time to explain any natural phenomenon which people
couldn't comprehend long time ago.
Encouraged by my experience of healing DM patients I dare to explain DM
without IR and IS.
Recall at the historical observations
Let's take a look at observations shared commonly by all DM patients.

1. No DM patient has proper hemorheology.
--This is result of enjoying modern life. No one oppose this
proposition though no one sticks it out with it. There may be some one
claiming cholesterol indicators are more important than hemorheology.
The fact is that there we can see occasionally DM patients with proper
cholesterol indicators. This implicates that hemorheology is closely
related with DM. When hemorheology is not in order tissues wouldn't
get enough oxygen. It implicates oxygen may have its part in formation
of DM.
2. Blood lactate level of DM is about 3 times that of normal people. As
lactate is only metabolite of glycolysis tissues of DM patients undergo
severe oxygen debt. (Take look at Table 2)
Table 1:On the approach to measuring the lactate concentration between
plasma of DM patient and anemia patient and plasma of normal people and
blood donors
DM patients
(n=7aging 30~60) Anemia Patients
(n=9Aging 20~60) Healthy People
(n=15aging 20~50) Blood donor
(n=28aging 20~30)
(472215)mgL-1 (340125)mgL-1 (13031
)mgL-1 (14746)mgL -1)
(Reference: measuring of blood lactate in DM patient and Anemia
patient, Vol. 21, 3rd, 2000, Journal of 4th melitary medical U. by Li
xiaohua, Wu hong, Jiang ru, Liu wei, and Xu bing)
3. Debility is shared by all DM patients. This symptom is observed even
after sugar level is normalized, which implicates DM is about more than
so called insulin resitance. This also implicates DM patients
couldn't generate lasting amount of energy. When oxygen is in debt
cells are no way to generate lasting amount of energy.
4. When drinking alcohols DM patients can enjoy short time of normal
life, perfectly normal like a healthy man. Alcohols boost hemorheology.
This implicates proper hemorheology is perfectly helpful for DM
patients. Proper hemorheology can surly deliver rich oxygen to tissues.
Can delivery of rich oxygen make sugar level normal?
5. Glucagon level of DM patients is all in high altitude. When
glucagons climb up sugar level is definitely going up as glucagons are
for mobilization of fuels, right contrary to insulin. It is rationale
to say that when glucagons are stronger than insulin sugar level goes
up and up.
Items of 1, 2, 3, and 4 above all finger at issue of oxygen debt. Could
DM be direct result of hypoxia of tissues?
Discussion:
It should be noted that hypoxia here is about tissues in debt other
than air lacking oxygen. When blood gets oxygen less than enough during
pulmonary cycle, like instances in plateau or anemia, body will call up
compensation mechanism to makeup the shortage, like increasing rate of
pulse and breathing, and/or generating more of RBC. What would the body
take when tissues falls in hypoxia?
Glucose is metabolized in two forms in body: Glycolysis to result in 2
molecules of lactate while oxygen is in short; Oxidation to result in 6
molecules of water and carbon dioxide while oxygen is sufficient. It is
worth to note that there is great gap between glycolysis and oxidation
in terms of energy generation. Glycolysis contributes only 2 ATPs while
oxidation 38. Let's think about this scenario.
In a moment, a cell needs 380 ATPs to meet its biological demand. If
all these energy is derived by oxidation it needs 10 molecules of
glucose and 60 molecules of oxygen to generate 380 ATPs exactly. What
if oxygen available is 5% less than enough? As a matter of fact,
glycolysis could be the only option to makeup the difference. Let's
make a simple calculation. As oxygen available is 57(60x95%) only 9.5
molecules of glucose could be oxidized. As a result 361 ATPs are
generated. To generate another 19 ATPs by glycolysis another 9.5
molecules of glucose has to be put into consumption since one molecule
of glucose contributes only 2 ATPs by way of glycolysis. As a result 5%
shortage in oxygen results in 19 molecules of glucose in total to
generate 380 ATPs which could be delivered merely 10 molecules of
glucose when oxygen supply is sufficient. Translated, it is 90%
increase in glucose consumption. Would the body meet this big demand?
In philosophical view, body will do its best to assist tissues generate
enough energy. Body has 3 options to do so.
aAdjust blood and vessel to make more oxygen permeate through
membrane of cells, which is surly impractical at all. So, body has
another 2 options to take.
bPut more fuel, primarily glucose, into blood stream, which could be
realized by increasing secretion of glucagons and adrenaline.
cAssist cells increase efficiency in acquiring glucose, which must
be realized by secreting more insulin.
--a, b, and c of above are termed DanTai Effect in whole.
DanTai effect is definitely have the effect of high level of insulin
and high level of glucagons with possibly normal level of glucose,
which is obviously the reality with people in the beginning phase of
progression to DM. In other words, when tissues fall in oxygen debt
body calls up DanTai effect. At the beginning phase of progression to
DM, the strength of glucagons and insulin is in balance. When this
balance doesn't stand sugar level either goes down or up. We discuss
the latter case as it is exactly what we call DM. Why the balance
between insulin and glucagons loose their ground at last? This is due
to mechanism of glucagons secretion.
On the other hand high blood sugar works negatively to oxygen delivery
mechanism. High sugar level promotes RBC aggregation by glycating RBC
and activates fibrinogen to worsen the hemorheology. Translated, higher
blood sugar level boosts more severe hypoxia, as worsened hemorheology
curtails oxygen transportation, which in turn results in higher blood
sugar level. As a result, when this fashion lasts long DM is definitely
going to be formed.
The analysis above is plausible in philosophical view, but as observed
clinically not all people, such as hypertension patients or thrombus
patients, with improper hemorheology gets DM. The reason lies in the
mechanisms of insulin secretion and glucagons secretion.
Sure, we expounded etiology of DM without reference to IR or IS. Should
we say DM is irrelevant with IS or IR, both of which are descriptive
and inclusive terms other than scientific terms.
Mechanisms of insulin and glucagons
Hypertension patients and thrombus patients suffer from worsened
hemorheology. However they could escape from claw of DM. Therefore we
can conclude worsening of hemorheology not necessarily results in DM.
But DM is most likely result of chronic hypoxia of tissues. Answer to
this phenomenon could be found in mechanisms of insulin and glucagons.
Cohort in Manchester U. made a great experiment back in 1989, the
thesis of which was published in Biochem. J. (1989) 259, 507-511. The
thesis could be referenced by this link:
http://www.TaoPanacea.com/Archives/InsulinSecretion.Pdf. The statement
below is quoted from the thesis:

The secretion of insulin from perfused rat pancreatic islets was
stimulated by raising the glucose concentration from 5.6 to 20 mm or by
exposure to tolbutamide. The addition of sodium lactate (40 mM) to
islets perfused in the presence of glucose (5.6 mM) resulted in a
small, transient, rise in the rate of secretion. The subsequent removal
of lactate, but not glucose or tolbutamide, from the perfusate produced
a dramatic potentiation of insulin release. The rate of efflux of
45Ca2" was also increased when islets were exposed to a high
concentration of glucose or lactate or to tolbutamide, and again
subsequently upon withdrawal of lactate. Efflux of 86Rb+ was modestly
inhibited upon addition of lactate and markedly enhanced by the
subsequent withdrawal of lactate from islets. The output of ["4C]
lactate from islets incubated in the presence of [U-'4C] glucose
increased linearly with increasing concentrations of glucose (1-25 mM).
It is proposed that the activation of islets by the addition or
withdrawal of lactate is not due to increased oxidative flux, but
occurs as a result of the electrogenic passage of lactate ions across
the plasma membrane, resulting in islet celldepolarization, Ca2" entry
and insulin secretion. The production of lactate via the glycolytic
pathway, and the subsequent efflux of lactate from the islet cells with
concomitant exchange of H+ for Na+, could be a major determinant of
depolarization and hence insulin secretion, in response to glucose.

Their conclusion is "The efflux of lactate from the islet cells could
be a major determinant of depolarization and hence insulin secretion,
in response to glucose". The more fast the lactate is discharged from
islet cell the more secretion of insulin is resulted. I term their
observation as Lactate Theory of Insulin Secretion (LTIS). LTIS could
explain neatly about the insulin curves extracted from DM patients,
which is still confuses professionals in the field though. DM
patient's basal insulin level is about 10% higher than normal people
while their insulin level trails far behind that of normal people
postprandial (Take a look at Table 2).
Table 1: The change of glucagon level and insulin level at fasting
state and after taking 100g of dimsum(x s)
Group Item Fasting After taking 100g of Dimsum(t/min)
30Min 60Min 90Min 120Min
Control Group
(n=34) Glucagon(/ng
L-1) 65.23.7 68.95.2 58.34.6 46.34.2 43.23.8
Insulin(z/mU
L-1) 7.31.2 53.77.1 68.28.7 28.97.9 10.02.6
Insulin/Glucagon 11.61.4 51.23.8 61.57.8 36.55.2 15.53.0
Diabetes Group
(n=65) Glucagon(/ng
L-1) 85.36.1** 98.36.9** 113.18.5** 98.08.6** 81.57.8**
Insulin(z/mU
L-1) 8.42.8 1.72.6** 18.02.6** 19.33.0** 14.22.4*
Insulin/Glucagon 9.21.3 10.51.8** 14.81.6** 17.21.3* 16.92.5
Comparing with control group*t=2.012.33
P<0.05;**t=6.78~26.58,P<0.01;comparing fasting state
F=2.25~15.45,q=3.91~4.32,P<0.05 q=4.78~6.83, P<0.01
(Reference: Clinical significance of the change of glucagon and insulin
in DM 2. Vol. 39 third, Journal of Medical school of QingTao U.)

1) DM patients produce far more lactate than normal people in basal
condition, about 3 times that of normal people, so it is likely that
their islet cells discharge lactate in higher rate, resulting in higher
secretion of insulin in basal situation;
2) After meal, normal people undergo steep elevation of glucose level.
High level of sugar curtails significantly the delivery of oxygen to
islet cells. As a result, big volume of lactate production in islet
cells is made, resulting in secretion of insulin 5~6 times their basal
insulin level. Since DM patient's sugar level is positioned high even
before the meal, therefore glucose elevation is less steep than normal
people postprandial, hence the milder change in oxygen delivery,
resulting in less steep elevation in lactate production in islet cells.

3) Blood lactate level of DM patients is close to 3 times that of
normal people; therefore lactate from islet cells of DM patients is
more difficult to come out.
Above 3 reasons explain why DM patient have their insulin level curve
far different from that of normal people. We could infer that the
longer islet cells suffer from hypoxia the less reactive to sugar
level. When this situation goes on, the secretion of insulin could be
impaired and glucagons might be in better position.
Let's sit upon the mechanism of glucagons now.
The conventional wisdom tells us ATP/AMP value in tissue dictates
secretion of glucagons. As glucagons are secreted by -islet cells the
proper proposition should be "ATP/AMP value in -islet cells
dictates secretion of glucagons". When ATP/AMP value goes down, like
in the case of -islet cells falling in oxygen debt, the secretion of
glucagons is promoted. When severity of hypoxia, like in the case of
DM, overrides the gain of ATP due to elevation of sugar level the
secretion of glucagons becomes rampant. As a result glucagons get upper
hand than insulin at last. That's DM.
It should be noted here that in case worsened hemorheology of blood
stream is not expressed in vessel web of islet cells both insulin
secretion and glucagons should be in order while other parts of body
suffer from hypoxia. This is why thrombus or hypertension patients
could escape from DM. But it is sure when hemorheology gets worse to a
point where islet cells are choked of hypoxia meaningfully DM would be
guaranteed. .
There seems other reason as well. We have to note that DanTai effect
mobilizes high volume of insulin secretion and glucagons secretion,
which is pathological in fact. Can DanTai Effect stay in use without
damaging islet cells? The reality is islet cell is susceptible to
damage as clinically demonstrated by many DM patients. When damage is
suffered more than 85% DM type 1 is realized. When islet cell get
damaged the secretion of insulin is very likely negatively effected.
When this damage helps glucagons get upper hand DM is also guaranteed.
The treatment
>From elucidations above we can tell DM is result of chronic islet
hypoxia. Accordingly treatment should be for improving delivery oxygen
to islet cells. When islet cells get sufficient oxygen the value of
ATP/AMP goes up and the secretion of glucagons becomes down and down
and gives its way to insulin like in the normal fashion. Meanwhile the
secretion of insulin would be close to normal as well and it is great
pleasures to human kind were islet cell could recover bit by bit in
this case.
To deliver sufficient oxygen to islet cells, the only practical way is
to improve hemorheology of the whole blood system. In fact, the
improvement of blood hemorheology results in healing or cure of
hypertension, thrombus, and many other cardio-vascular diseases.
Therefore treatment of DM is most difficult thing to do. Can there be
such magic thing that could help blood get back to its old time happy
condition?
Through our great amount of effort and endeavor, we come up with an
herbal remedy, Oxygen Booster, which delivers magic result in improving
blood hemorheology. We have a measure for efficacy for Oxygen Booster.
One should feel fresh in brain and vigorous around the body after
taking Oxygen Booster Capsule. As sugar curtails delivery of oxygen DM
patients should take bigger dose of Oxygen Booster along with chemical
medicine (Metformine the best while one has no weakest liver) or
insulin injection. In any case to see the sign of working---fresh brain
and vigor in body-- that Oxygen Booster works well is paramount
prerequisite. Within 30~60 days after Oxygen Booster delivers efficacy
one can get his/her hemorheology normalized.
Oxygen Booster delivers magic result which couldn't be explained by
conventional wisdom. This is the direct cause of making new theory of
DM etiology come to birth.
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