Chronic Hypoxia of Islet cell results in Diabetes Mellitus
Chronic Hypoxia of Islet cell results in Diabetes Mellitus
by ChengTai Zhu
The links below endorse partly my claim that DM is result of hypoxia by worsened hemorheology.
1. Hypoxia Acutely Induces Glucose Intolerance
http://www.taopanacea.com/Archives/H...ntolerance.htm
2. Whole-blood viscosity and the insulin-resistance syndrome
http://www.TaoPanacea.com/Archives/BloodViscosity.htm
3. Anemia Common Among Diabetics
http://www.taopanacea.com/Archives/A...gDiabetics.htm
4. COPD A Risk Factor for Type 2 Diabetes
http://www.taopanacea.com/Archives/C...e2Diabetes.htm
5. Effect of Experimental Diabetes Mellitus on Plasma Lactate
http://www.taopanacea.com/Archives/E...smaLactate.pdf
6. Effects of lactate on pancreatic islets
http://www.TaoPanacea.com/Archives/InsulinSecretion.pdf
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?
Encouraged by my experience of healing diabetics I dare to elucidate DM without IR and IS.
Recall at the historical observations
Let??s take a look at observations shared commonly by all diabetics.
1. No DM patient has proper hemorheology.
????This is result of luxury of modern life. No one opposes this proposition though no one sticks it out with it. Some people claim that cholesterol indicators are more important than hemorheology. The fact is that there we can see occasionally diabetics with proper cholesterol indicators. This implicates that hemorheology is closely related with DM. 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 diabetics undergo severe oxygen debt. (Take a look at Table 1)
3. Debility is shared by all diabetics. This symptom is observed even after sugar level is normalized, which implicates DM is about more than so called insulin resitance. This also implicates diabetics 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 diabetics can enjoy short time of normal life, though the next day it brings deteriorated sick. Alcohols boost hemorheology. This implicates proper hemorheology is probably helpful for diabetics.
5. Glucagon level of diabetics 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.
6. Basal insulin level of type 2 diabetics is absolutely higher than that of healthy people while diabetics trail far behind healthy people postprandial in terms of insulin level.
(??look at this link, http://www.TaoPanacea.com/Archives/DataE.htm.)
Items of 1, 2, 3, and 4 above all finger at issue of oxygen debt. Could DM be direct result of hypoxia of tissues? 5 and 6 could find their answers in the mechanism of insulin secretion and glucagon secretion.
Discussion:
It should be noted that hypoxia is about tissues in oxygen debt other than air lacking oxygen.
Glucose is metabolized in two forms: Glycolysis to result in 2 molecules of lactate with contribution of 2 ATPs of energy while oxygen is in short; Oxidation to result in 6 molecules of water and carbon dioxide with contribution of 38 ATPs while oxygen is sufficient. Let??s think about this scenario.
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? 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 with 361 ATPs contributed. 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. Translated, it is 90% increase in glucose consumption. 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.
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 definitely has the effect of high level of insulin and high level of glucagons(endorsed by 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.
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 of insulin may not exist at all.
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.
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 faster the lactate is discharged from islet cells the more secretion of insulin is resulted. Their observation could explain neatly about the insulin curves of both healthy people and diabetics, 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 2).
1) Diabetics produce far more lactate than normal people in basal condition, 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 produce 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,
b) High level of sugar curtails significantly the delivery of oxygen to islet cells. Though this effect is on to both diabetics and healthy people the latter amy under go far more steep curve because their hemorheology was in normal. As a result, big volume of lactate production in healthy peopls' islet cells is made.
c) Peripheral tissue fluid of islet cells of diabetics maintains high level of lacate and scattered islet cells are so diployed to properly sense the change of lactate level around them.As a result, diabetics get more resistance than healthy people when discharging lactate from islet cells.
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.
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 α-islet cells the proper proposition should be that ATP/AMP value in α-islet cells dictates secretion of glucagons?. When ATP/AMP value goes down, like in the case of α-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.
In case worsened hemorheology is not expressed in peripheral tissue fluid 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 that when hemorheology gets worse to a point where islet cells are choked meaningfully DM would be guaranteed.
β islet cell is susceptible to damage as clinically demonstrated by many diabetics. When this damage helps glucagons get upper hand.
The treatment
I have come up with the conclusion through application of Oxygen Booster, if you agree with view point above your inquiry on OB is welcome.
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