Diabetes and vanadium

Problem of DM

In the postwar period, rapid growth of industrialization has led to the replacement of manual labor to mechanical and this inevitably led to hypodynamy and as a result to obesity. During physical activity a large amount of energy is derived primarily from the absorption of carbohydrates, and accompanied by a decrease in blood sugar. Muscles at work utilize glucose, even in the absence of insulin.

The second factor has increased the number of diabetics — more abundant food, alas, largely at the expense of carbohydrates.

Also, heredity plays a significant role in the emergence and development of diabetes — 12% of newly diagnosed patients have close relatives with diabetes. Diabetes type 2 occurs most frequently, and in some countries reaches 80% of all cases.

Over time, diabetes can infect the heart, blood vessels, eyes, kidneys and nerves.

  • Diabetic retinopathy is an important cause of blindness and occurs as a result of long-term accumulation of damage to small blood vessels in the retina. After 15 years of diabetes, approximately 2% of people blind, and about 10% develop severe visual impairment.
  • Diabetic neuropathy is a nerve lesion due to diabetes, and affects up to 50% of patients with diabetes. Although diabetic neuropathy can also result in various problems, the usual symptoms are tingling, pain, numbness or weakness in hands and feet. In conjunction with the reduction of blood flow neuropathy of legs increases the probability of ulcers on the legs and, ultimately, amputation.
  • Diabetes is among the leading causes of kidney failure. From renal failure, 10%–20% of patients dead are those with diabetes.
  • Diabetes increases the risk of heart disease and stroke. From cardiovascular diseases (mainly heart disease and stroke), 50% of patients die from diabetes.
  • The overall risk of fatal outcome among diabetics is at least two times higher in risk of death than those who are not diabetes.

There are more than 246 million people suffering from diabetes in the world. If the current trend continues in the future, by 2020 the world will have about 350 million diabetics. The forecast is unfavorable for Americans: every third or every second resident of a minor born in the new millennium will get sick with diabetes during their lifetime. Since 1987, the death rate from diabetes rose by 45%, while deaths from heart disease, vessels of the brain (stroke) and cancer decreased slightly. Maintaining normal blood glucose, cholesterol, and blood pressure decreases, albeit to varying degrees, risk of heart attacks and stroke. Annual routine examinations (ocular fundus vessels, evaluation of arterial blood flow in the vessels of the legs), as well as regular monitoring of blood pressure can prevent the development of serious complications of diabetes: blindness, gangrene of lower limbs, acute and chronic vascular diseases of the heart, kidneys, brain. According to WHO projections, if in the next 10 years are not taken urgently; the number of deaths from diabetes will increase by more than 50%. In 2006–2015 it is forecasted that there will be more than 80% increase in the number of deaths from diabetes in countries with middle high income.


The facts of diabetes
  • Diabetes currently affects 246 million people worldwide and is expected to grow to 380 million by 2025.
  • In 2007, five countries with the largest number of people with diabetes are India (40.9 million), China (39.8 million), USA (19.2 million), Russia (9.6 million) and Germany (7.4 million).
  • In 2007, five countries with the highest prevalence of diabetes among the adult population of Nauru (30.7%), United Arab Emirates (19.5%), Saudi Arabia (16.7%), Bahrain (15.2%) and Kuwait (14.4%).
  • By 2025, the largest increase in the prevalence of diabetes will be in developing countries.
  • Each year 7 million people become sick with diabetes.
  • Each year recorded 3.8 million deaths related to diabetes. Even more died from cardiovascular disease, such as complications of diabetes-related lipid disorders and hypertension.
  • Every 10 seconds a person dies from diabetes-related causes.
  • Every 10 seconds two people develop diabetes.
  • Diabetes is the fourth leading cause of death globally.
  • At least 50% of all people with diabetes are unaware of their condition. In some countries this figure may reach 80%.
  • Up to 80% of diabetes type 2 can be prevented by adopting healthy diet and increasing physical activity. Diabetes is a major cause of kidney failure in developed countries and is the cause of the huge costs of dialysis.
  • Type 2 diabetes has become one of the most frequent causes of renal failure in humans in Western countries.
  • 10% to 20% of people with diabetes die of kidney failure.
  • It is estimated that more than 2.5 million people worldwide suffer from diabetic retinopathy.
  • People with type 2 diabetes are twice as likely to get heart attack or stroke as people who do not have diabetes. Indeed, people with type 2 diabetes suffer from a heart attack as people without diabetes who already have heart attacks.


Vanadium effect was first studied and described by Hiromiti Okuda, MD, a professor at the University of Kumamoto, Japan. Professor Hiromiti Okuda revealed the ‘secret’ capability of vanadium to reduce the glucose concentration in the blood.


Method of control of glucose concentration in the blood and highlights of pathogenesis of insular diabetes

Our organism contains about 60 trillion cells. We receive nutrition and energy using those elements which come from food. The main energy sources are carbohydrates, fats and proteins. Carbohydrates are the most important energy source; they are extracted from food and then converted to glucose in the liver, and then delivered to the muscles, adipose tissue and other organs by the blood stream. As the glucose concentration increases (as a result of eating), the hormone — insulin, which is secreted in the pancreas (in β-cells) by the islets of Langerhans, activates. Insulin forwards glucose from the blood to the muscular and fat cells — so called insulin-dependent tissues. Glucose in a cell is used for energy generation or deposited as a glycogen in the liver. A healthy man has the glucose concentration in his blood come to norm in 1–2 hours after food intake. As the glucose concentration in the blood (normally) reduces, the α-cells of the islets of Langerhans generate glucagon (a hormone), which splits glycogen accumulated in the liver. Therefore, the glucose concentration in the blood increases. Insulin and glucagon are two hormones, which are secreted in the pancreas and regulate the glucose concentration in the blood. With insulin-independent (type II) diabetes, insulin is generated in normal or even higher quantity, but the mechanism of interaction of insulin with the cells is disturbed (insulin resistance). The main reason for the insulin resistance is the disorder of membrane insulin receptors, as a rule, in case of obesity (the main health hazard). This disorder means that the receptors are incapable of interacting with the hormone because of change in their structure and quantity. Some types of insulin-independent (type II) diabetes are characterized with the possible disorder of insulin structure (genetic defect). Besides obesity, the other health hazards for insulin-independent (type II) diabetes are elderly age, cacoethes, arterial hypertension, chronic overeating and sedentary life. The diabetes of this type, in general, involves patients above 40. In Japan, insulin-independent (type II) diabetes patients are 95% of the insular diabetes patients. Regardless of the pathogenic mechanism, the common for all types of diabetes is the constant increase in the glucose concentration in the blood and metabolism disorder, when the tissues are not able to seize glucose and use it for the purpose specified. Tissue inability to use glucose results in hypercatabolism of fats and proteins and ketoacidosis. The rise in the glucose concentration in the blood results in the osmotic pressure increase, which causes severe fluid and electrolyte loss when urinating. The constant increase in the glucose concentration in the blood has negative effect on the state of many organs and tissues, which in the end results in severe complications such as: diabetic nephropathy, neuropathy, ophthalmopathy, micro- and macroangiopathy, various types of diabetic coma and other. The insular diabetes patients show the decrease in the immune system reactivity and the severe course of infectious diseases. The most important problem is insulin-independent (type II) diabetes, when an organism does not accept insulin secreted largo manum (some sources say that insulin-independent (type II) diabetes rate is about 80% of the total diabetes patients). Pathogenesis of insulin-independent (type II) diabetes is still a subject of intensive researches today. There is no doubt that three main mechanisms: β–cell malfunction, disorder of the insulin-mediated glucose seizure by the target tissues, and glucose generation by the liver, are involved in this pathology development. But the question which component plays a leading role and which are the consequences, albeit very important, is still under discussion. The many years’ laboratory researches and clinical studies have proven biological effects of vanadium-contained compounds (hypoglycemic and insulin-saving activity, insulin sensitivity increase and cholesterol concentration reduction and other) as a therapeutic agent in insulin-independent (type II) diabetes. The USA, Canada and Japan consider the vanadium-contained compounds today as the potential antidiabetic agents imitating insulin effect.

So why does inorganic vanadium have the same properties as insulin does?

Based on Professor Okuda’s findings, the so-called ‘insulin receptor’ theory is erroneous. It means that the insulin receptor has no relation to the glucose activity.

The role of insulin in reduction to the glucose concentration in the blood is widely known, but few people know about the insulin receptor and the insulin receptor theory.

The thumbnail of the insulin receptor theory:

1. Insulin carried by the blood comes to α-sub-block of the insulin receptor on a cytoderm surface.

2. Upon insulin arrival to the α-sub-block, β-sub-block protein (transmembrane located) on the opposite side of receptor is phosphorylated and the receptor is activated.

The most interesting property of the insulin receptor, which distinguishes it from other receptors of protein- and peptide-origin hormones, is its ability to autophosphorylate, when the receptor itself has protein kinase (tyrosine kinase) activity. When insulin is bonded with the α-chain of receptor, the tyrosine kinase activity of β-chains is activated by means of phosphorylation of their tyrosine remains. Active tyrosine kinase of β-chains, by turn, activates the chain of phosphorylation-dephosphorylation of protein kinase, in particular, of membrane or cytosolic serine- or threonine kinase, i.e. of protein kinase and target proteins, in which phosphorylation is made by means of OH-groups of serine and threonine. Accordingly, the change in cytolergy occurs, in particular, enzyme activation and inhibition, glucose transport, synthesis of supermolecule of the nucleic acid and proteins. But the fine molecular mechanisms of signal transfer from the insulin-receptor complex to the existing variety of intracellular processes have not been revealed yet. Some intracellular second messengers, in particular, cyclic nucleotides, derivatives of phosphatidyl inositols and other are possible to participate in these processes. Besides, the possibility of the existence of an intracellular intermediate or a mediator of insulin effect (a special intracellular receptor), which controls the gene transcription and the mRNA synthesis may not be denied. Insulin effect and participation in the gene expression regulation or in some specific mRNA transcription is supposed to explain its [insulin] role in such fundamental life processes as embryogenesis and the higher organism cell differentiation.

3. The receptor receives information about activation, and the intracellular GLUT4 glucose carrier moves to cytoderm.

4. GLUT4 — glucose carrier from the blood associates with glucose and transports it into a cell.

The above is a thumbnail of the insulin receptor theory, which describes the ‘insulin receptor — insulin’ relation, which activity result is the reduction in the glucose concentration in the blood.


The clue is in the ‘Na+/H+ channel’

Professor Hiromiti Okuda’s statement is reasoned and justified. First, the cohesion (bond strength) between insulin and insulin receptor, which [the cohesion] was studied as follows. Usually, any hormone and its receptor when interacting are bonded tightly, as a lock and a key, such bond is called the hydrophobic bond. First, insulin was colored with a fluorescent pigment and bonded to a cell receptor. Then the receptor-insulin bond was washed with water with temperature 4C. This resulted in the insulin-receptor bond, when washed with water with temperature 4C, was destroyed after the first washing, which meant the weak insulin-receptor bond. At the same time the suspension of glucose transport from the blood into the cell was confirmed. This cell was afterwards bonded one more time with the fluorescent pigment colored insulin, which resulted in the renewal of glucose transport from the blood to the cell. Based on these findings, Professor Okuda concludes that ‘no doubt that insulin initiates the glucose transport from the blood to a cell’. Insulin and its receptor are in ion bond. Second, it is the pH change in intercellular fluid. With intercellular fluid of pH 7.4, insulin and the receptor have the largest cohesion degree, and the glucose transport from the blood to a cell runs normal. But, with insulin close to the cell receptor and in enough quantity, if the intercellular fluid pH is 7.2, the glucose transport reduces by 50%, and with pH 7.0 the transport stops. Up to this day scientists believe that if insulin coheres with the receptor, glucose goes from the blood to a cell without problems. Based on Professor Hiromiti Okuda’s findings, despite the bond between insulin and cell receptor, with the intercellular fluid pH below 7.4, the glucose transport from the blood to a cell reduces or stops completely. It proves that the insulin receptor theory is not the only thing that explains the glucose transport from the blood.


Mechanism of the glucose transport from the blood to a cell.

What the mechanism of glucose transport from the blood to a cell is. If the glucose transport from the blood to a cell depends on the intercellular fluid pH, then there is something which maintains and affects this process. That was why Professor Hiromiti Okuda drew his attention to the role of Na+/H+ channel in the glucose transport to a cell, the operation depending directly on pH rate both inside and outside a cell. ‘Sodium’ is a sodium ion (Na+,sodium ion), ‘Hydrogen’ is a hydrogen ion (H+,hydrogen ion), ‘Channel’ is a canal meaning gates.



How the Na+/H+ channel operates.

When this channel operates, sodium ion (Na+), which is outside the cell, enters into the cell, and hydrogen ion (Н+), which is inside the cell, goes outside the cell — into the intercellular space. A healthy man has the cell pH 6.8 — weak acidity, the intercellular fluid pH 7.4 — weak alkali, the pH level depends on the hydrogen ion concentration. The fact that this channel is activated by insulin was discovered 20 years ago. But since the international attention was concentrated on the insulin receptor theory, the role of the Na+/H+ channel as a part of glucose transport from the blood to a cell was ignored. When insulin operates in the channel, sodium ion gets into a cell and hydrogen ion gets outside the cell at the same time. In this case, the intracellular pH changes from 6.8 to 7.0. As the pH rate increases, calcium ion bonded to cytoderm is isolated, which initiates the glucose transportation with GLUT4 glucose carrier, which [GLUT4] moves to cytoderm, bonds to glucose and moves glucose inside the cell.

If the Na+/H+ channel does not operate, even with enough insulin available, insulin-independent (type II) diabetes is going to develop.

The researches showed that the intercellular fluid pH, which facilitates the glucose transport from the blood to a cell, is changing as affected by vanadium. The pH, as affected by vanadium, increases by +0.2, i.e. turns towards an alkali, and activates the Na+/H+ channel, which, afterwards, activates indirectly the GLUT4 glucose carrier. Therefore, with the reduction in the intercellular fluid pH, there is the reduction in the effectiveness of the Na+/H+ channel, and, as a result, the reduction in insulin effect on the initiation of glucose transport to a cell. The insulin atomic weight is 6000, when the same of vanadium is 50.9415. Besides, vanadium is inorganic, so vanadium is possible to activate the channel operation much better than insulin does.

95% insular diabetes patients in Japan are type II diabetics, it means that type II diabetics give no response to insulin; this state is called the high insulin resistance. In Professor Hiromiti Okuda’s opinion, the high insulin resistance may be explained by the fault in the Na+/H+ channel only. In other words, if the Na+/H+ channel operates, glucose comes to the cells, and the glucose concentration in the blood reduces.


Vanadium is the insulin mimetic agent

International researches proved that vanadium when interacting with the insulin signal system (on the receptor or post receptor levels) imitates the insulin metabolic effects with intensifying this hormone sensitivity and extending the effect of biologic tissue response to insulin.

Any substance or agent having the same effect as insulin does is called the insulin mimetic action.

Based on his test results, Professor Hiromiti Okuda studied vanadium effect on fat metabolism. In his experiment he studied the degree of vanadium effect on fat metabolism in a fat cell, particularly, on the lipogenesis processes. He used the following vanadium concentrations: 1μМ, 10μМ, 100μМ and 1000μМ.

As a result of this test, the intensity of lipogenesis processes started changing with 1μМ concentration, and the lipogenesis intensity increased with the increase in vanadium concentration. If to compare the lipogenesis intensity with the vanadium concentration 1μМ and 1000μМ, the process intensity increased almost by 2.



We must say that the vanadium effect on lipogenesis, as shown in the diagram, was studied without insulin participation, i.e. the lipogenesis process proceeded due to vanadium only.

The next test demonstrates the vanadium capability to inhibit the lipolysis processes. The test studied the intensity of lipolysis processes with the hormones such as: norepinephrine and ACTH (adrenocorticotropic hormone), with vanadium present. Norepinephrine and ACTH initiate the lipolysis process and the fat breakdown, and it results in free fatty acids.

Therefore, if vanadium is able to inhibit the hormone activities, there should be few free fatty acids, compare with the lipolysis process with either norepinephrine or ACTH present.

Method: Vanadium and the hormones — norepinephrine and ACTH — were immersed successively into a buffer fluid, and the rats’ fat cells were added.

Test 1: What happens in case of norepinephrine-vanadium combination



The test results showed that the intensity of lipolysis process (fat breakdown) retarded with 10μM vanadium concentration present. As the vanadium concentration increased, the lipolysis (fat breakdown) process retarded more and more.

Test 2: The same test was conducted with ACTH. The results showed the lipolysis restriction with the vanadium concentration 1μМ. The free fatty acids, when added 1μМ vanadium, were half of that was generated with ACTH present without vanadium added.



Tests 1 and 2 demonstrate the vanadium effect restraining the lipolysis processes with both norepinephrine and ACTH present. This effect is the same as what insulin does, which make us state with sure that vanadium is the insulin mimetic agent.


Vanadium is the strongest insulin mimetic agent

(Professor Hiromiti Okuda, MD)

Based on the test results, the following conclusions were made —

Vanadium is an inorganic substance with the following capabilities:

1. To initiate and optimize the glucose transport to a cell and, at the same time, to increase insulin sensitivity.

2. To inhibit the lipolysis process, without insulin and with the hormones promoting lipolysis.

In the studies of vanadium effect on the metabolism processes, the focus was made on the vanadium capability to inhibit the lipolysis process.

Given that the insular diabetes first affects fat metabolism, and that the main predisposing factor for insulin-independent (type II) diabetes is overweight (obesity), all these caused some additional tests to study the vanadium effects on fat metabolism.

First, let us have a short look at pathology of disbolism when insular diabetes.

When there is insular diabetes, lipid disbolism combines with changes of postprandial level of some lipids and, in particular, of triglyceride. One of the reasons for this process is insulin resistance, which every insulin-independent (type II) diabetes patient has in a varying degree. If, normally, insulin suppresses the free fatty acid release from a fat depot after food intake, then insulin resistance disturbs this suppressive function of insulin, which results in increase in the concentration of free fat acids in the liver and rise in the number of particles which are very low-density lipoproteins (VLDL). There are some changes in the particle pattern and the tendency to increase in the large VLDL or VLDL1 particles containing a lot of triglycerides. VLDL1 is a chylomicron analog, which [chylomicrons] are released from the liver of a healthy man in case of hunger or lack of lipids coming with food. With a healthy man, the meal inhibits the release of such large particles and, therefore, ensures continuous balance between VLDLs coming from intestine and those VLDLs released from the liver. With insulin-independent (type II) diabetes, there is a continuous disbalance of two component VLDLs, as VLDLs continue coming in plenty from the liver and in case of hyperinsulinemia as a reaction to the meal. There are some changes in LDL particle pattern, in particular, the small dense particles increase and the large particles decrease. The small dense LDL particles have more sensitivity to damaging actions of free radicals. And the high linolenoic acid concentration in them results in their acidification. Besides, the cholesterol ester/free cholesterol ratio increases and the phospholipid/protein ration reduces, and the LDL acidification and the LDL protein glycosylation increase. Cholesterol reduces as well, and the changes in the HDL particle pattern are revealed, which is accompanied with some certain increase in small HDL particles (HDL3) and reduction in the large HDL particles (HDL2); the LDL particles containing triglyceride increase; the LDL-contained proteins and the apolipoprotein A-1 concentration reduce. There is the increase in the unesterified fatty acid concentration and the reduction in the postprandial capability of insulin to inhibit their level, which is caused by insulin resistance of adipose tissue. Insulin resistance in the liver results in reduction in inhibiting effect of insulin on the VLDL release.

Excessive fat retention and cholesterol generation in the liver results in hyperproduction of β-lipoprotein and dislipidemia, and promotes atherosclerosis.

On the other hand, as a result of the above, the fatty liver infiltration promotes acetonemia — ketone bodies uptake in the blood; ketone bodies are suboxidized products of fat metabolism (acetoacetic acid, beta-hydroxy-butanoic acid, acetone), which result in reduction in alkaline reserve in the blood and the acidosis process, which, in its turn, promotes tissue protein breakdown.

Based on the above, the reduction in alkaline reserve in the blood results finally in insulin incapability to take its complex and many-sided physiologic effects, most of which are performed through the insulin capability to take effect on some enzyme activities, such as:

1. Insulin is the only hormone reducing the glucose concentration in the blood. This is made in the following way:

  • increase in the cellular absorption of glucose and other matters;
  • activation of key glycolysis enzymes;
  • increase in the glycogen synthesis intensity — insulin forces glucose storage in hepatocytes and myocytes by glucose polymerization in glycogen;
  • reduction in gluconeogenesis intensity — reduces glucose production from various matters in the liver.

А. Anabolic effects

  • increases cellular absorption of amino acids (especially, leucine and valine);
  • increases the potassium ion, magnesium and phosphate transports into a cell;
  • increases DNA replication and protein biosynthesis;
  • increases fatty acid synthesis and subsequent etherification — insulin in the adipose tissue and liver promotes glucose transformation into triglycerides; with lack of insulin the reverse process takes place — fat mobilization.

B. Anticatabolic effects

  • suppresses proteolysis — decreases the protein degradation;
  • reduces lipolysis — reduces fatty acids to the blood.

Based on the above, we may conclude the following: insulin deficiency or insulin resistance results in disturbance of the glucose penetration in tissues and the reduction in glucose depositing as glycogen in the liver. Moreover, so-called “energy hunger” of tissues occurs as a result of disbolism, which [the energy hunger] results in the increase in glycogen transformation into glucose, which launches fat disbolism. The result of the above is dislipidemia, hyperglycemia and glycosuria (the presence of excess sugar in the urine). The next stage of pathogenesis of basal metabolism, when there is insular diabetes, is the glucose synthesis from amino acids (neoglycogenesis), which results in disorder of protein synthesis. This, finally, results in consumption.

An adult has a fixed number of adipocytes (fat cells), and this number does not increase, but the size of adipocyte is capable of enlarging (hypertrophy). That is why overeating and hypodynamia, which leads to disbolism, result in increase in weight — obesity.

In 1994 Professor Hiromiti Okuda, MD, managed to extract an undamaged adipose drop from adipocyte and determine the mechanism of natural fat breakdown (lipolysis).

Normally, the adipose drop surface is coated with lecithin, which impedes lipase (lipolysis enzyme) effect, i.e. no lipolysis occurs.

With obesity, the surface area of adipocyte enlarges, but the number of lecithin does not increase, and there occur ‘cracks’ in the lecithin membrane, which bond with lipase and initiate lipolysis.

Therefore, the lipolysis process will continue until adiposyte decreases and the lecithin density regenerates; so, while the hypertrophy process exists, the lipolysis process will continue, accordingly.

The test results demonstrate that the more the adipocyte diameter the more intensive the lipolysis process is and the more decay products.

But the increasing concentration of lipolysis products minces insulin action, resulting in the vicious circle of pathogenesis.

In Professor Hiromiti Okuda’s opinion, this is exactly the insulin-independent (type II) diabetes.

The following test demonstrates that, in the instances of natural fat breakdown (lipolysis), the inhibition of the lipolysis process failed even with the use of large insulin doses.

This test used adipocytes; 6 one week old rats (adipocyte dia is 40μm), 8 one week old rats (adipocyte dia is 60μm) and 10 one week old rats (adipocyte dia is 70μm). The quantity of insulin was adjusted for the purpose to find the number of insulin capable of inhibiting the lipolysis process.



Result — negative, even with the large insulin concentrations.

In contrast to the test using vanadium, where 1μМ concentration inhibited the lipolysis process.

The tests and experiments have proven the vanadium capability to retain the process of natural fat breakdown, even with low vanadium concentration.

Insulin, normally, may inhibit the lipolysis process with the help of hormones, but it is not able to retain the natural fat breakdown occurring with insulin-independent (type II) diabetes (Professor Hiromiti Okuda), the cause of which [disease] is the overweight — obesity.

Eventually, vanadium activates and optimizes the Na+/H+ channel, by improving the glucose activity in the cells, and vanadium not only reduces the glucose concentration in the blood, but also impedes the generation of free fatty acids, which are the cause of insulin-independent (type II) diabetes, and vanadium cures radically insular diabetes.


All the above is from research materials by Professor Hiromiti Okuda, MD.