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Deadly Substances Causing Diabetes Complications-Ultimate Glycosylated Proteins (AGEs)-Smoking

Care健康志  2011/01  p46~p47        Text: Liu Yongxiang, General Manager of Hengshengxing Biotechnology

At noon on last Saturday’s holiday, I was preparing to go out for lunch with my family. The phone rang, and Mr. A’s voice "I am in the emergency room" came out. After a moment, the sound was normal. After asking about the hospital, he rushed inside. In the emergency room of Lake Medical Center, the doctor in the emergency room said that Mr. A’s heart stopped beating, and he was rescued with electrodes just now. My heart was SOS. Mr. A was lying on the bed and looked at me and said, chest tightness, back pain, and breathing difficulties. His daughter Added that less than 20 minutes after arriving in the emergency room, I was in a coma. It was a myocardial infarction. I urgently received a cardiac catheterization and installed a stent. After one day of observation in the intensive care unit, he was transferred to the general ward. In the ward, Mr. A was full of breath. I said, fortunately, I fell in the emergency room. If I fell at home, it would be dangerous. I smiled and did not answer. Mr. A is a martial artist. He is healthy, his blood test and blood pressure are all normal, but he smokes cigarettes. It is very big, with a smoking age of more than 35 years, I suddenly thought of the final glycated protein (AGEs).

In diabetic patients, under high blood sugar conditions, glucose in the blood will naturally combine with protein, lipid, and nucleic acid in the blood through the Mener reaction ( Maillard Reaction), will produce a large amount of Advanced Glycosylation End product (AGEs) in the blood. This final Glycosylation End product (AGEs) will cause inflammation, which is the killer of the complications of diabetes. The final glycated protein (AGEs) in the blood will be combined with the final glycated protein donor (AGE-Receptor, RAGE) on the vascular endothelial cells, and then combined with HMGB1 (amphoterin) will immediately trigger an acute inflammatory response. Complications of cardiovascular disease (hypertension, atherosclerosis), kidney disease (dialysis), eye disease (cataract), peripheral nerve injury, etc. These are typical complications of diabetes.

Huebschmann et al.’s 2006 medical paper counted 100 AGEs-positive patients, of which about 20-30% were not diabetic patients. These 20-30% of the patients had high AGEs concentration (positive The source of reaction) is from smoking and eating foods with high AGEs content.

Smoking does cause an increase in blood AGEs. A medical paper published by CERAMI et al. in 1997 showed that both tobacco extracts and smoking smoke extracts contain glycotoxin, which is a kind of High reactive glycation products can quickly combine with proteins to produce AGEs and also induce gene mutations.

Hyperglycemia in the blood of diabetic patients takes about several weeks to several months to form AGEs in the body; glycotoxins in tobacco are inhaled in large quantities into the alveoli, and then absorbed into the blood and combined with proteins , It only takes a few hours to quickly produce AGEs. CERAMI's medical papers, one of the experiments is to detect the comparison of AGEs in the blood of smokers and non-smokers. The experimental results show that the blood AGEs content of smokers (210.6 ± 51 AGE unit/ml) is higher than that of non-smokers (161.6 ±). ; 53 AGE unit/ml) is 30% higher.

The large amount of AGEs produced by smoking will cause inflammation, which will develop into atherosclerosis in the long run. Medical papers published by predecessors revealed that the number one fatal disease caused by smoking is myocardial infarction, and other smoking-related diseases include peripheral vascular diseases, cerebrovascular diseases and other diseases.

During the health check, it is necessary to check whether the concentration of AGEs in the blood is normal. Patients who are positive for AGEs will be screened and given appropriate treatment for lowering AGEs, or their lifestyle habits (quit smoking or diet) will be adjusted , Will be able to effectively prevent the occurrence of cardiovascular and other diseases.

Reference:

1. CARLA CERAMI etl Proc. Natl. Acad. Sci. USA, Vol. 94, pp. 13915–13920, December 1997, Medical Sciences
2. Robbins, S. L., Kumar, V. & Cotran, R. S. (1994) in Pathological Basis of Disease (Saunders, Philadelphia), 5th Ed., pp. 379–430.
3. Shah, P. K. & Helfant, R. H. (1988) Chest 94, 449–452.
4. Sherman, C. B. (1991) Clin. Chest Med. 12, 643.
5. Vlassara, H., Fuh, H., Makita, Z., Krungkrai, S. & Cerami, A. (1992) Proc. Natl. Acad. Sci. USA 89, 12043–12047.
6. Brownlee, M., Cerami, A. & Vlassara, H. (1988) N. Engl. J. Med. 318, 1315–1321.
7. Bucala, R., Model, P., Russel, M. & Cerami, A. (1985) Proc. Natl. Acad. Sci. USA 82, 1670–1674.
8. Lee, A. T. & Cerami, A. (1987) Mutat. Res. 179, 151–158.
9. Lee, A. T. & Cerami, A. (1987) Proc. Natl. Acad. Sci. USA 84, 8311–8314.
10. Lee, A. T. & Cerami, A. (1990) Mutat. Res. 238, 185–191.
11. Bucala, R., Makita, Z., Koschinsky, T., Cerami, A.&Vlassara, H. (1993) Proc. Natl. Acad. Sci. USA 90, 6434–6438.
12. Bucala, R. & Cerami, A. (1996) in The Maillard Reaction: Consequences for the Chemical and Life Sciences, ed. Ikan, R. (Wiley, Philadelphia), pp. 161–181.

(Latest edition) The killer of diabetes complications-AGEs (Final Glycosylated Protein)

Causing complications of diabetesMurder– AGEs (Final Glycosylated Protein)

Diabetes

The so-called diabetes means that the concentration of blood glucose (glucose) is too high to exceed the standard value. After the doctor confirms that you are diabetic, the doctor will use blood sugar lowering (insulin) drugs to try to control your blood sugar within the normal value. At the same time, the doctor will also test your glycosylated hemoglobin (HbA1c) to see if your blood sugar control is good or not in the past few months, or test Glycated Alibumin (GA) to see the blood sugar control status in the past 2 weeks. The reminder you should avoid food, take medicine on time, and control blood sugar well.

The killer of diabetes complications

Although you worked hard to cooperate, with the passage of time, it was accompanied by the emergence of complications, and it seemed that no one was spared. You have high blood pressure, proteinuria, blurred vision, more serious cases, such as cardiovascular disease (arteriosclerosis, myocardial infarction, stroke), kidney failure (uremia), dialysis, cataracts, peripheral neuropathy, etc. Diabetic patients seem to have no Fortunately, it's just a difference in speed and severity. Thanks to science and technology and nearly 40 years of research efforts, the culprit responsible for the complications of diabetes has been found, that is, AGEs (ultimate glycosylated proteins) that are abnormally elevated in the blood.

Final glycated eggFormation of white and Mena reaction

The mystery of the complications of diabetes has finally been solved by scientists. The final glycated protein (Advanced Glycosylation End Product, AGEs) is the deadly killer of the complications of diabetes. The final glycated protein (AGEs or AGE) is also called glycation. End product or advanced glycation end product. In diabetic patients, when the blood is at a high concentration of glucose, the carbonyl group of glucose in the blood binds to the amino group of arginine or lysine on protein, nucleic acid or fat, and directly undergoes glycation reaction. The entire saccharification reaction process is also called Maillard Reaction (Maillard Reaction), and the final products of this reaction are called final glycated proteins (AGEs).

Final glycated proteinReaction with inflammation

When the final glycated protein (AGEs) appears in the blood, the final glycated protein (AGEs) will bind to the AGEs Receptor (final glycated protein receptor) on vascular endothelial cells and produce superoxide radicals, which are activated AGEs Receptor combined with HMGB1 (High Mobility Group Box-1) and S-100 ⁽¹¹⁾ will directly induce an inflammatory response, which will lead to systemic cardiovascular disease, kidney disease, cataract, Peripheral neuropathy is currently considered to be one of the main factors of diabetic complications^(3、16,17). Cells with AGE receptors in humans include Endothelial Cell blood vessel, smooth mucle cell blood vessel, Podocyte foot cell (kidney), Astrocyte/Microglia astrocyte/nerve, Monocyte /Macrophage(immune system)⁽¹²⁾. Podocytes located in the glomerulus are specifically responsible for filtering. When free AGEs combine with the AGE receptors on the podocyte membranes, an inflammatory response is generated, which makes the podocytes ineffective in filtering and allows proteins to escape. The microalbumine/urine protein is positive ⁽¹³⁾; the first layer of blood vessels is endothelial cells. When the second layer of smooth muscle cells combine with AGE to produce an inflammatory response, resulting in smooth muscle cell proliferation, Homocysteine ​​will increase. , The proliferation of vascular smooth muscle cells causes the vascular wall to bulge to form plaques (Plaque)⁽¹⁴⁾; when AGE attacks the elastin of the blood vessels, it will harden and lose its elasticity, causing blood pressure to rise; the literature points out that AGE causes Vascular lesions, atrophy and necrosis are one of the causes of male sexual insufficiency ^{(19, 20)}. Evidence shows that the brain of Alzheimer’s disease deposits a large amount of amyloid (starch-like substance), and AGE is its precursor. Body ( Precursor)⁽¹⁸⁾, AGE causes cataracts, and also attacks Cornea, Vitreous, and Retina to cause related lesions⁽¹⁵⁾ , ------ -.

Final glycosylated proteinExcretion

AGEs are mainly excreted through the kidneys. AGEs can be bound by the clearance receptors of specific cells, decomposed into amino acids and small molecule peptides through catalysis, and then excreted by the kidneys. Most kidney cells include endothelial cells, renal tubular cells, glomerular cells, and pseudopodia Blood cells all contain the AGE clearance receptor, including AGE-R1, AGE-R2, and AGE-R1. -R3), and the phagocytic cell clearance receptor (MSR) includes SR-AII, SR-BI and CD-36. The literature pointed out that when the kidney starts dialysis, the concentration of AGE in the blood will increase by 50 times.

What are the reasons for the increase in the concentration of final glycated protein (AGEs) in the human body?

1) Hyperglycemia in the blood of diabetic patients is the main cause of the increase in AGEs in the body.

2) Ingested from food, for example: drinking foods high in AGEs, including fried, grilled and pickled foods.

3) Medical literature also shows that smoking is another important source of increasing AGEs in the body.

Final glycated protein detection and monitoring

As the final glycated protein (AGEs) is the killer of the complications of diabetes, it has become an important task to detect the presence and concentration of AGEs in the blood. Early detection of abnormal rise of AGEs in the blood is important. It allows you to detect the inflammatory response of blood vessels caused by AGEs at the earliest possible time, so as to achieve the purpose of early detection and early treatment. The monitoring of the final glycated protein (AGEs) concentration can be used as a therapeutic indicator. Therefore, detecting the concentration of AGEs in the blood is currently an important indicator for monitoring the complications of diabetes.

Using drugs or active ingredients to eliminate AGEs in the blooddiabeticsThe most direct and effective way to block inflammation and complications is the most direct and effective way to block inflammatory reactions and complications.

The effective ingredients or drugs that reduce the concentration of AGEs in the blood? and the principle of action?

1.) Effective ingredients or drugs to prevent the formation of AGEs: ALT946, LR90, OPB9195, PARP inhibitor, B6 (Pyridoxamine),    Aminoguanidine, Benfotiamine, AR inhibitors, etc.

2.) Effective ingredients or drugs that destroy AGEs crosslink: PTB (N-phenacylthiazolium bromide), ALT711, etc.

3.) Anti-hypertensive drugs (can also lower AGEs):  ARB, ACE inhibitor, etc. 4.)  AGEs binding agent: Soluble RAGE, Lysozyme, etc.

5.) Antioxidants: Green Tea, Vit. E, Vit. C, etc. 6.) Oral hypoglycemic drugs (can also lower AGEs): Metformin, Pioglitazone.

Other natural ingredients that have been published in the literature that can eliminate/block the formation of AGEsinclude:

Tomato paste (tomato paste), Resveratrol (resveratrol), inositol (inositol), Carnosine (carnosine), Curcumin (curcumin), Rosemary (rosemary), Alpha-lipoic acid (α- Lipoic acid), Flavonoids luteolin (flavonoid compound luteolin), rutin (rutin), quercetin (quercetin), kaempferol (kaempferol), Ginger (ginger), Cinnamon (cinnamon), Cumin (cumin) .

As the final glycated protein (AGEs) in the formation of diabetes complications and the mechanism of complication, it has been confirmed in experiments by researchers around the world in the past 30 years that it can prevent the formation of AGEs and eliminate AGEs in the blood. The ingredients (drugs) of the drug have become a matter of concern to everyone at once. Through the research of scientists and the input of pharmaceutical companies, the drugs or effective ingredients related to the elimination (reduction) of the final glycated protein (AGEs) have been discovered one after another, and some are in progress. In clinical human trials, some of the existing drugs have the ability to lower the final glycated protein (AGEs), some have been sold in the market, and some are natural ingredients. It is worth mentioning that Benfortiamine (B1 The fourth phase of the clinical trial of the derivative) has ended with excellent results. It is waiting for the approval of the US FDA to become the first AGE-lowering drug candidate of the US FDA. The Hanson AGEs Test test reagent produced by Hengshengxing Biotechnology Co., Ltd. It can measure the concentration of AGEs in the patient's blood at any time. It is an important monitoring tool. In addition, the oral hypoglycemic drugs Metformin, Pioglitazone, and Atorvastatin approved by the FDA have the ability to lower AGEs. They are all great experimental results and messages. All of these will enable medical staff to be more capable of caring for and educating people with diabetes, thereby improving the quality of life and life expectancy of people with diabetes. Let us work together.

Reference material:

1. Kidney International(1999) 55, 389–399     2. Current Alzheimer Research, Volume 1, Number 1, February 2004 , pp. 39-46(8)

3. Diabetes Care 29:1420-1432, 2006         4. Glycobiology vol. 15 no. 7 pp. 16R–28R, 2005

5. Cardiovascular Diabetology 2008, 7:29      6. Cardiovascular Diabetology 2002, 1:1

7. Circulation Research. 2004;95:233-238       8. Am J Hypertens. 2004 Dec;17(12 Pt 2):31S-38S

9. Nature 414, 813-820 (13 December 2001)   10. Clin Biochem Rev. 2005 November; 26(4): 123–134.

11. Kidney International (1999) 56, S54–S56    11. Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):164-70  

12. Cell Mol Biol 1998, 44:1013-1023          13. Nephrol Dial Transplant (2008) 23: 2179–2191

14. Exp Clin Cardiol Vol 7 No 1 Spring (2002)   15. Br J Ophthalmol 2001;85:746–753

16. Lab Invest 1994;70:138–51.                17. Martin Dunitz, 1999:67–92

18. J Neural Transm 1998;105:439–61.          19. World J Urol 1995;13:369–75

20. Urology 1997;50:1016–26. 

The comparison of current stem cell

(Autologous P-Stem Cell)

The comparison of current stem cell

AGEs Vs HbA1c

AGEs Vs HbA1c

Ideal Diabetes Complications Treatment Method-Comparison of Diabetes and Its Complications Treatment

Comparison table of traditional diabetes treatment and ideal diabetes B6 treatment

Computer information of the final glycated protein (AGEs test) reagent

Thank you for your support for Hengshengxing Biotechnology in the past few years. Hanson AGEs tests have been able to directly access the automatic biochemical analyzer and obtain the experimental results in 10 minutes. This quantitative value can be used as a treatment indicator under long-term tracking. Currently available biochemical analyzers include Hitachi, Toshiba, Olympus and Beckman models. For related information, please contact the sales department, thank you. Thank you for your support for Hengshengxing Biotechnology in the past few years. Hanson AGEs tests have been able to directly access the automatic biochemical analyzer and obtain the experimental results in 10 minutes. This quantitative value can be used as a treatment indicator under long-term tracking. Currently available biochemical analyzers include Hitachi, Toshiba, Olympus and Beckman models. For related information, please contact the sales department, thank you.

The relationship between Advanced Glycosylation End Product (AGEs) and dialysis patients

Text: Liu Yongxiang, General Manager of Hengshengxing Biotechnology There are three sources of increased AGEs in the blood. 1. Diabetes patients 2. Smokers 3. People who eat fried and grilled foods. The final glycated protein concentration in the blood of normal people is very low. The long-term abnormal increase in the concentration of AGEs in the blood will immediately cause systemic vascular inflammation, and the blood vessels will die for a long time, leading to organ diseases, including atherosclerosis, hypertension, myocardial infarction, stroke, kidney disease (nephritis), kidney Failure (dialysis), cataracts, retinopathy, peripheral nerve damage, etc., no diabetic patient can escape this spell before. The AGEs in the blood will be excreted through the action of the kidneys to maintain the health of the body. For dialysis patients, the function of the kidneys to excrete AGEs will be greatly reduced, or even lose this function, which means that the blood of diabetic dialysis patients The concentration of AGEs is extremely high, and the progress of its complications is rapid. The final glycated protein (AGEs) can be washed out by hemodialysis or peritoneal dialysis. This is very important for dialysis patients. It is determined that AGEs in the blood of dialysis patients are washed out, which will directly reduce/slow the harm of complications, and then Extend the life span of dialysis patients.