View Full Version : Chronic Hypoxia of Islet cell results in Diabetes Mellitus (the newest)

February 26th 06, 05:07 PM
Chronic Hypoxia of Islet cell results in Diabetes Mellitus (the newest)
Authored by ChengTai 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 reactions, 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 glycosylates red blood cells (RBC) to make it loose electrical
polarity, as a result RBCs aggregate. 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£¨out of control, the
However, not all worsened hemorheology results in DM, demonstrated by
those suffering hypertension or/and thrombus. This is duo to the
mechanism of secretion of insulin and glucagons. Insulin secretion is
dictated by the rate of lactate effluent from •‚ cell islet. The
secretion of glucagons is dictated by the stock of ATP and AMP in •Š
islet cell, other than other in other tissue cells.
the links following endorse partly our claim that DM is result of
hypoxia by worsened hemorheology.
1. Hypoxia Acutely Induces Glucose Intolerance

2. Whole-blood viscosity and the insulin-resistance syndrome
3. Anemia Common Among Diabetics
http://www.taopanacea.com/Archives/AnemiaCommonAmongDiabetics.htm )
4. COPD A Risk Factor for Type 2 Diabetes
5. Effect of Experimental Diabetes Mellitus on Plasma Lactate
http://www.taopanacea.com/Archives/EffectofExperimentalDiabetesMellitusonPlasmaLactat e.pdf

6. Effects of lactate on pancreatic islets
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 reminds me 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 opposes 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. Tissues of DM discharge more lactate than healthy people. As lactate
is only metabolite of glycolysis it is sure that tissues of DM patients
undergo severe oxygen debt. (Take look at Table 2)
Table 2: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 Anemia Patients Healthy People Blood donor
(n=7£¨aging 30~60) (n=9£¨Aging 20~60) (n=15£¨aging
20~50) (n=28£¨aging 20~30)
(472°ĺ215)mg°§L-1 (340°ĺ125)mg°§L-1 (130°ĺ31
)mg°§L-1 (147°ĺ46)mg°§L -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 probably 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?
It should be noted that hypoxia here is about tissues in oxygen debt
other than air lacking oxygen. When blood gets oxygen less than enough
during pulmonary cycle, like instances in people coming to plateau
terrain or in 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%) molecules
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,
suprisingly enough 5% shortage in oxygen results in 19 molecules of
glucose in total to generate 380 ATPs which could be delivered merely
10 of glucose in the case that oxygen supply is sufficient. Translated,
it is 90% increase in glucose consumption. How 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.
a£©Adjust blood and vessel to make more oxygen approach and permeate
through membrane of cells, which is surly impractical at all. So, body
has another 2 options to take.
b£©Put more fuel, primarily glucose, into blood stream, which could be
realized by increasing secretion of glucagons and adrenaline.
c£©Assist 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(endorsed the fact that glycogenolysis in
this phase is highly active ) 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 in reality. At the beginning phase of
progression to DM, the strength of glucagons and insulin is in balance,
which is the reason why people in this situation keep normal level of
glucose and high insulin level, so called insulin resistance. It is
obvious to me that so called IS is result of high level of glucagons.
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?
On the other hand high blood sugar works negatively to oxygen delivery
mechanism. High sugar level promotes RBC aggregation by glycosylating
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 have so far 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.Further
more, resistance and sensibility may not exist at all.
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 definitely 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 of both healthy people and DM
patients, which 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 1).
Table 1: http://www.taoPanacea.com/Archives/DataE.htm
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. Translated, DM secretes more
insulin than normal in basal state.
2) After meal, healthy people undergo steep elevation of lactate
effluent caused by 3 reasons below:
a)Tissues of healthy people produces lactate in higher rate than DM.
After meal, sugar level climbs steep slope for both healthy people and
DM.And Better hemorehology can deliver more glucose at higher
speed.This results in steep elevation in lactate production, more with
healthy people, worsened by reason b) following.
b)High level of sugar curtails significantly the delivery of oxygen to
islet cells. Though this effect is on to both DM patients and healthy
people the latter amy under go far more sttep curve because their
hemorheology was in normal.As a result, big volume of lactate
production in healthy peopls' islet cells is made, resulting in
secretion of insulin 5~6 times their basal insulin level.
c) Peripheral tissue fluid of DM maintains high level of lacate and
scattered islet cells are so diployed to properly sense the change of
lactate level around them. Obviously, patients is close to 3 times that
of normal people; therefore lactate from islet cells of DM patients are
far more difficult to diffuse out from inside than healthy people's.
Above reasons explain why DM patient have their insulin level curve far
different from that of healthy people. We could infer that the longer
islet cells suffer from hypoxia the less reactive to sugar level
change. 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 tissues dictates secretion of glucagons. As
glucagons are secreted by •Š-islet cells the proper proposition should
be that ATP/AMP value in •Š-islet cells dictates secretion of
glucagons". When ATP/AMP value goes down, like in the case of
•Š-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 peripheral tissue fuluid around islet cells
both insulin secretion and glucagons should be in order while other
parts of body suffer from hypoxia resulted from bad hemorheology. 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 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 effect 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 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. When insulin
takes helm the sugar level begins to dip until it is low enough to make
the ATP store in •Š-islet cell gets down to a point where the secretion
of glucagons are activated. It is essential for a proper glucose
metabolism that insulin and glucagons rotates in taking the helm for
glucose dispose in blood.

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 DM be
cured. The answer is: sure, with 3 exceptions.1)Peripheral tissue fluid
of islet cells are made not to be perfused improperly, congenital in
most cases by genetic cause;b)•‚ islet cell is damaged badly,
espeicially when more than 85%, like type 1. c) Mitochondria of islet
cell is out f work.

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,