Diabetes oxidation

Methylpyrazine-2- Glipicide Anti-diabetic Oxidation Pseudomonas putida Single-stage fermentation [6]... 

T. Yokozawa, H. Y. Kim, and E. J. Cho, Erythritol attenuates the diabetic oxidative stress through modulating glucose metabolism and lipid peroxidation in streptozotocin-induced diabetic rats, J. Agric. Food Chem., 2002, 50, 5485-5489. 

Answer Individuals with uncontrolled diabetes oxidize large quantities of fat because they cannot use glucose efficiently. This leads to a decrease in activity of the citric acid cycle (see Problem 17) and an increase in the pool of acetyl-CoA. If acetyl-CoA were not converted to ketone bodies, the CoA pool would become depleted. Because the mitochondrial CoA pool is small, liver mitochondria recycle CoA by condensing two acetyl-CoA molecules to form acetoacetyl-CoA + CoA (see Fig. 17-18). The acetoacetyl-CoA is converted to other ketones, and the CoA is recycled for use in the /8-oxidation pathway and energy production. 

Other measures for monitoring oxidative stress include superoxide dismutase, glutathione peroxidase, catalase, glutathione, glutathione disulphide, and glutathione reductase. The oxidation of LDL has been implicated in the development of cardiovascular diseases and diabetes. Oxidized LDL can be measured using... 

Alloxan (1003) has been observed in the mucus associated with dysentery and it was the very first pyrimidine made synthetically when Brugnatelli oxidized uric acid in 1818. Alloxan has an interesting diabetogenic action which appears to be associated with removal of essential zinc from insulin by chelation. Such permanent diabetes may be induced in fish, dogs, cats, sheep, some birds, monkeys and other creatures, but not in man, owls or guinea-pigs certain pyrimidines related to alloxan show some such activity. 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

Geen tea Camellia sinensis Reduces cancer, lowers lipid levels, helps prevent dental caries, antimicrobial and anti oxidative effects Contains caffeine (may cause mild stimulant effects such as anxiety, nervousness, heart irregularities, restlessness, insomnia, and digestive irritation) Contains caffeine and should be avoided during pregnancy, by individuals with hypertension, anxiety, eating disorders, insomnia, diabetes, and ulcers. 

Mortensen PB. C6-C10-dicarboxyUc aciduria in starved, fat-fed and diabetic rats receiving decanoic acid or medium-cbain triacylglycerol. An in vivo measure of the rate of beta-oxidation of fatty acids. Biochim BiophysActa, 1981, 664(2), 349-355. 

Increased fatty acid oxidation is a characteristic of starvation and of diabetes meUims, leading to ketone body production by the Ever (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia. This occurs in various states of carnitine deficiency or deficiency of essential enzymes in fatty acid oxidation, eg, carnitine palmitoyltransferase, or inhibition of fatty acid oxidation by poisons, eg, hypoglycin. 

A second principle used widely for glucose analysis, is that of the oxidation of glucose enzymatically, mediated by the action of glucose oxidase with the formation of gluconic acid and hydrogen peroxide (22). In this procedure it is the hydrogen peroxide which is usually assayed for determination of glucose. This method suffers from the action of inhibitors which occur, particularly with patients in a diabetic coma and these need to be removed. 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

Hunt, J.V., Dean, R.T. and Wolff, S. (1988). Hydroxyl radical production and autoxidative glycosylation. Glucose oxidation as the cause of protein damage in the experimental glycation model of diabetes mellitus and ageing. Biochem. J. 256, 205-212. 

Hunt, J., Bottoms, M. and Mitchinson, M.J. (1993). Oxidative alterations in the experimental glycation model of diabetes mellitus are due to protein-glucose adduct oxidation. Biochem. J. 291, 529-535. 

Collier et al. (1990) extended their studies relating to oxidative stress and diabetes by demonstrating that the levels of several free-radical scavengers (red cell superoxide dismutase, plasma thiols) were significantly reduced in 22 type 2 diabetic patients (mean age 53 years) in comparison with 15 control subjects (mean age 51 years). No significant diflFerences in red cell lysate thiols or... 

In a recent study, serum ascorbate concentrations were significantly reduced in a group of elderly diabetic patients (w = 40, mean age 69 years) in comparison with an age-matched group of non-diabetic controls ( = 22, mean age 71 years), and this reduction was more pronounced in those patients with microangiopathy (Sinclair et al., 1991). Diabetic patients were shown to have a high serum dehydroascorbate/ascorbate ratio indicative of increased oxidative stress. Ascorbate deficiency was partially corrected by vitamin C supplementation, 1 g daily by mouth, but the obvious disturbance in ascorbate metabolism in the diabetic patients was accentuated, since serum ascorbate concentrations fell (after the initial rise) despite continued vitamin C supplementation (Fig. 12.3). 

It should be remembered that some of the established antioxidants have other metabolic roles apart from free-radical scavenging. The finding of reduced antioxidant defences in diabetes, for example, may not be prima fascie evidence of increased oxidative stress, since alternative explanations may operate. For example, this may reflect a response to reduced free-radical activity as su ested by the results of a previous study (Collier et al., 1988). In the case of ascorbate, an alternative explanation has been proposed by Davis etal. (1983), who demonstrated competitive inhibition of ascorbate uptake by glucose into human lymphocytes. This view is supported by the similar molecular structure of glucose and ascorbic acid (see Fig. 12.4) and by a report of an inverse relationship between glycaemic control and ascorbate concentrations in experimental diabetes in rats. Other investigators, however, have not demonstrated this relationship (Som etal., 1981 Sinclair etal., 1991). 

Other considerations such as demonstrating a direct correlation between the level of oxidative stress and tissue damage in diabetes and showing that antioxidant therapy leads to prevention, arrest or regression of diabetic complications are also important and must be the basis of future well-designed studies. 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

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