Reducing lipid peroxidation stress of erythrocyte membrane by alpha-tocopherol nicotinate plays an important role in improving blood rheological properties in Type 2 diabetic patients with retinopathy.

The effects of alpha-tocopherol nicotinate on blood viscoelasticity and viscosity and on lipid peroxidation stress in erythrocyte membranes in patients with Type 2 DM were investigated. Thirteen Type 2 diabetic subjects with retinopathy were given alpha-tocopherol nicotinate 300 mg tds, after meals, for 3 months. The treatment resulted in significant reductions of blood viscosity at different shear rates (e.g. -2.23 +/- 2.82 p<0.015, gamma = 1.5 s(-1)) and viscoelasticity (p<0.004); resistance of erythrocyte deformation (p<0.001) and lipid peroxidation stress in red cell membrane (malondialdehyde or MDA reduced by 0.17 +/- 0.13 nmol l(-1) p<0.005). Plasma viscosity, red cell rigidity, and HbA1c were unchanged. There were negative linear correlations between the indices of red cell deformability and the levels of MDA Diabetes is a significant health care problem in the US that results in substantial morbidity and mortality. In 1997, an estimated $44 billion was spent on direct and indirect medical expenditures attributable to diabetes. It is well recognized that interventions that slow or alter the progression of diabetes could have a significant impact on the health care costs associated with this disease. Nutrients including Vitamin E , Vitamin C , Magnesium, Chromium , Lipoic Acid , and Vanadium have all been shown to have a beneficial effect on the symptoms or complications associated with diabetes. Many of these nutrients appear to be closely associated with insulin metabolism and help maintain proper blood glucose levels of red cell membrane both pre- and post-treatment (e.g. R = -0.79, p<0.001; R = -0.78, p<0.002, n = 13; pre- and post-, respectively). We suggest that the improvements of rheological properties of blood and red cell deformability by alpha-tocopherol nicotinate are mainly attributed to reducing lipid peroxidation stress on membranes of red blood cells. The treatment may be useful in slowing deterioration of microangiopathy in Type 2 DM.

Chung, T.W., Yu, J.J., Liu, D.Z. Department of Biomedical Engineering, Chung-Yuan Christian University, Chung-Li, Taiwan, China. Diabet Med 1998 May;15(5):380-5.

Effects of Momordica charantia fruit juice on islet morphology in the
pancreas of the streptozotocin-diabetic rat.

An investigation was made of the effect of Momordica charantia fruit juice on the distribution and number of alpha, beta and delta cells in the pancreas of streptozotocin (STZ)-induced diabetic rats using immunohistochemical methods. The results indicated that there was a significant (Student's t-test, P < 0.004) increase in the number of beta cells in Momordica charantia -treated animals when compared with untreated diabetics, however, their number was still significantly less than that obtained for normal rats. There was also a significant (P < 0.006) increase in the number of delta cells in STZ-diabetic rats compared to non-diabetic rats. This increase in the number of delta cells was not affected by Momordica charantia treatment. The number of alpha cells did not change significantly in Momordica charantia -treated rats when compared with untreated diabetic rats. Our results suggest that oral feeding of Momordica charantia fruit juice may have a role in the renewal of beta cells in STZ-diabetic rats or alternately may permit the recovery of partially destroyed beta cells.

Ahmed, I., Adeghate, E., Sharma, A.K., Pallot, D.J., Singh J. Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. Diabetes Res Clin Pract 1998 Jun;40(3):145-51.

Antidiabetic effect of a leaf extract from Gymnema sylvestre in
non-insulin-dependent diabetes mellitus patients.

The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in controlling hyperglycaemia was investigated in 22 Type 2 diabetic patients on conventional oral anti-hyperglycaemic agents. GS4 (400 mg/day) was administered for 18-20 months as a supplement to the conventional oral drugs. During GS4 supplementation, the patients showed a significant reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, and conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to discontinue their conventional drug and maintain their blood glucose homeostasis with GS4 alone. These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on GS4 supplementation. This is supported by the appearance of raised insulin levels in the serum of patients after GS4 supplementation.

Baskaran, K., Kizar Ahamath, B., Radha Shanmugasundaram K. Shanmugasundaram, E.R. Department of Biochemistry, Postgraduate Institute of Basic Medical Sciences Madras, India. J Ethnopharmacol 1990 Oct;30(3):295-300.

Evaluation of traditional plant treatments for diabetes:
studies in streptozotocin diabetic mice.

Seven plants and a herbal mixture used for traditional treatment of diabetes were studied in streptozotocin diabetic mice. The treatments were supplied as 6.25% by weight of the diet for 9 days. Consumption of diets containing bearberry (Arctostaphylos uva-ursi), golden seal (Hydrastis canadensis), mistletoe (Viscum album) and tarragon (Arte-misia dracunculus) significantly reduced the hyperphagia and polydipsia associated with streptozotocin diabetes, but bayberry (Cinnamo-mumtamala), meadowsweet (Filipendula ulmaria), senna (Cassia occidentalis) and the herbal mixture did not alter these parameters. Bearberry, mistletoe and tarragon retarded the body weight loss but none of the eight treatments significantly altered plasma glucose or insulin concentrations. These studies suggest that bearberry (Arctostaphylos uva-ursi), golden seal (Hydrastis canadensis), mistletoe and tarragon may counter some of the symptoms of streptozotocin diabetes without, however, affecting glycemic control.

Swanston-Flatt, S.K., Day, C., Bailey, C.J., Flatt, P.R. Department of Biological and Biomedical Sciences, University of Ulster, Coleraine, U.K. Acta Diabetol Lat 1989 Jan-Mar;26(1):51-5.

In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation.

BACKGROUND: Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation.

METHODS AND RESULTS: Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0.0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E  supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion.

CONCLUSIONS: We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

Davi, G., Ciabattoni, G., Consoli, A., Mezzetti, A., Falco, A., Santarone, S., Pennese, E., Vitacolonna, E., Bucciarelli, T., Costantini, F., Capani, F., Patrono, C. Departments of Medicine and Aging, University of Chieti "G. D'Annunzio" School of Medicine, Catholic University School of Medicine, Rome, Italy. Circulation 1999 Jan 19;99(2):224-9.

Diabetes-induced changes in lens antioxidant status,
glucose utilization and energy metabolism:
effect of DL-alpha-lipoic acid.

The study was aimed at evaluating changes in lens antioxidant status, glucose utilization, redox state of free cytosolic NAD(P)-couples and adenine nucleotides in rats with 6-week streptozotocin-induced diabetes, and to assess a possibility of preventing them by DL-alpha-lipoic acid. Rats were divided into control and diabetic groups treated with and without DL-alpha-lipoic acid (100 mg x kg body weight (-1) x day(-1), i.p.). The concentrations of glucose, sorbitol, fructose, myo-inositol, oxidized glutathione, glycolytic intermediates, malate, alpha-glycerophosphate, and adenine nucleotides were assayed in individual lenses spectrofluorometrically by enzymatic methods, reduced glutathione and ascorbate—colorimetrically, and taurine by HPLC. Free cytosolic NAD+:NADH and NADP+:NADPH ratios were calculated from the lactate dehydrogenase and malic enzyme systems. Sorbitol pathway metabolites were found to increase, and antioxidant concentrations were reduced in diabetic rats compared with controls. The profile of glycolytic intermediates (increase in glucose 6-phosphate and fructose 6-phosphate, decrease in fructosel, 6-diphosphate, increase in dihydroxyacetone phosphate, 3-phospho-glycerate, phosphoenolpyruvate, pyruvate, and no change in lactate), and 5.9-fold increase in alpha-glycerophosphate suggest diabetes-induced inhibition of glycolysis. Free cytosolic NAD+:NADH ratios, ATP levels, ATP/ADP x inorganic phosphate (Pi), and adenylate charge were reduced in diabetic rats while free cytosolic NADP+: NADPH ratios were elevated. Diabetes-induced changes in the con-centrations of antioxidants, key glycolytic intermediates, free cytosolic NAD+:NADH ratios, and energy status were partially prevented by DL-alpha-lipoic acid, while sorbitol pathway metabolites and free cytosolic NADP+:NADPH ratios remained unaffected. In conclusion, diabetes-induced impairment of lens antioxidative defense, glucose intermediary metabolism via glycolysis, energy status and redox changes are partially prevented by DL-alpha-lipoic acid. The findings support the important role of oxidative stress in lens metabolic imbalances in diabetes.

Obrosova, I., Cao, X., Greene, D.A., Stevens, M.J. Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0354, USA. Diabetologia 1998 Dec;41(12):1442-50.

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