Phytochemicals Treat Diabetic AGE
Herb Extracts Reduce Hyperglycemic Advanced Glycation Endproducts
Dec 15, 2008
Diabetics tend to progress toward a series of degenerative diseases (atherosclerosis, high blood pressure, disrupted peripheral circulation, blindness, arthritis, etc.) as high blood sugar levels, hyperglycemia, leads to chronic inflammation. A major consequence of hyperglycemia is an increased reaction between the blood sugar, glucose, and amino acids that make up the proteins of the blood serum, e.g. serum albumin and hemoglobin. The sugar-protein reaction is called non-enzymatic glycation and after several further spontaneous reactions, the results are advanced glycation endproducts, AGEs. AGEs bind to protein receptors found on cells throughout the body and trigger inflammation.
Blood Glucose is Regulated by Insulin
When glucose from food in the intestines or from glycogen in the liver, enters the blood and reaches a critical concentration, it triggers the release of insulin from the pancreas. Insulin makes more glucose transport proteins available on the surface of fat cells, adipocytes, and the blood glucose decreases as the fat cells import glucose and convert it into stored fat. A meal rich in starch causes a domino effect of physiological changes. There is a quick rise in blood glucose, followed by a quick rise in blood insulin. The insulin triggers a quick burst of fat production, a quick drop in blood sugar and hunger. It is difficult to lose weight on a starch-rich diet, because of rapid conversion of glucose to fat and constant hunger. A more modest, hypoglycemic meal with minimal starch would produce a modest increase in blood sugar without triggering an insulin response. Type I diabetics, who lack the ability to produce significant amounts of insulin, would not remove glucose from the blood effectively and the blood sugar level would just remain high (excreted in urine) while the cells of the body were starving for glucose.
Glucose at High Concentrations Chemically Reacts with Proteins
Glucose is quite reactive with other compounds in food, in blood and in cells. Sprinkling sugar on shrimp, for example, will make the shrimp brown more intensely when fried or grilled, because the sugar reacts with the proteins in shrimp juice and the product is brown. The same principle applies in browning meringues made of egg white and sucrose.
Plants, for example, produce very large amounts of reactive sugars in photosynthesis and avoid destructive reactions during transport of very concentrated sugars from leaves to roots, by transporting sucrose instead of glucose. In sucrose, the reactive atoms of two sugar molecules are joined to make a disaccharide, that is not reactive. Hence sugar cane and sugar maple display impressive concentrations of sucrose that can be squeezed from their stems or tapped from their trunks. Glucose cannot be transported the same way, because at very high concentrations, it would rapidly attack every protein that lines the blood vessels.
More Glucose in the Blood Means More AGE
Hyperglycemia accelerates the glucose reactions in blood, and serum proteins become decorated with attached glucose. The glucose attaches to the nitrogen atoms of the lysine amino acids of the serum proteins in the initial chemical reaction. The atoms in the new glucose-protein conjugates continue to rearrange until they reach stable configurations, advanced glycation endproducts, AGEs.
Proteins with AGE Attached Are Degraded and AGE Is Secreted
The body has a limited capacity to remove and secrete AGE. Some types of AGE are difficult for cells to process and they accumulate. Fructose is even more aggressive than glucose in forming AGEs and unfortunately the fructose AGEs interact with other proteins making chemical bridges between the proteins. High dietary fructose, for example, can cross-link collagen in the skin and accelerate visible aging. AGEs also trigger chronic inflammation and are involved in many inflammatory degenerative and autoimmune diseases. To duplicate human type I diabetes in mice, the mice are fed fructose and subsequent AGE-induced inflammation results in an immunological attack on insulin-producing pancreas cells.
Lower blood sugar over time produces less accumulated AGEs and lowers the risk of disease-causing chronic inflammation.
Traditional Herbs Block AGE Formation
The rate of AGE accumulation in diabetics is associated with kidney damage, nerve damage, retinopathy and cataracts. In traditional medicine, various herbs have been used to treat diabetes and its associated pathologies. In a recent study by M. Saraswat, et al., water extracts of seventeen herbs used in diabetes treatment were tested for their ability to inhibit AGE formation in laboratory experiments. Extracts of ginger, cinnamon and cumin were most effective, while black pepper, green tea, apple, basil and lemon extracts inhibited AGE only moderately. Ginger, cinnamon and cumin extracts were subsequently tested on AGE formation by fructose in laboratory experiments with eye lens proteins. Several biochemical tests were performed to measure the cross-linking of lens proteins that occurs during AGE formation with fructose. Ginger, cinnamon and cumin extracts were all effective in protecting the lens proteins from attack by fructose. These experiments demonstrate that herbs that are well tolerated in food may be the source of safe chemicals that are useful in therapy to reduce pathology associated with AGE formation in diabetes.
reference:
Saraswat M, Reddy PY, Muthenna P, Reddy GB. 2008 Prevention of non-enzymic glycation of proteins by dietary agents: prospects for alleviating diabetic complications.Br J Nutr. Nov 6:1-8.
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