Abstract
Previous research has suggested that type 1 diabetes mellitus may be due to oxidative
stress. The role of oxidative stress in type 2 diabetes is not known. Secoisolariciresinol
diglucoside (SDG) antioxidant, obtained from flaxseed, has been reported to prevent
type 1 diabetes in a rat model. However, its effectiveness in type 2 diabetes is not
known. An investigation was made of the effects of SDG isolated from flaxseed (40
mg/kg body wt, orally in drinking water) on the development of diabetes in Zucker
diabetic fatty (ZDF)/Gmi-fa/fa female rats, a model of human type 2 diabetes, to determine
whether this type of diabetes is due to oxidative stress and whether SDG could prevent
the development of diabetes. A total of 10 Zucker lean control and 26 ZDF rats were
used in this study. Incidence of diabetes was 100% in untreated and 20% in SDG-treated
ZDF rats by the age of 72 days (P < .01). The rats that did not develop diabetes by 72 days of age in the SDG-treated
group developed diabetes later on (age 72 to 99 days) except for 10% of the rats that
did not develop diabetes for the duration of the study (101 days of age), suggesting
that SDG retarded the development of diabetes. Diabetes was associated with an increase
in oxidative stress as suggested by an increase in serum malondialdehyde (P < .01). Also, diabetes was associated with an increase in serum total cholesterol
and triglycerides (P < .05) and glycated hemoglobin A1C (P < .05). ZDF rats treated with SDG that did not develop diabetes by 70 days of age
had no increase in oxidative stress, serum total cholesterol, and glycated hemoglobin.
These results suggest that type 2 diabetes is associated with an increase in oxidative
stress and that SDG is effective in retarding the development of diabetes. (J Lab
Clin Med 2001;138:32-9)
Abbreviations:
HbA1C (glycated hemoglobin), MDA (malondialdehyde), ROS (reactive oxygen species), SDG (secoisolariciresinol diglucoside), TC (total cholesterol), TG (triglycerides), ZDF (Zucker diabetic fatty)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults.Diabetes Care. 1998; 21: 518-524
- National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases: diabetes statistics. National Institute of Health, Bethesda (MD)1995: 1-4 (NIH publ no 96-3926)
- Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections.Diabetes Care. 1998; 21: 1414-1431
- Perspectives in diabetes: role of oxidative stress in development of complications in diabetes.Diabetes. 1991; 40: 405-412
- Lipid peroxidation and activity of antioxidant enzymes in diabetic rats.Mol Cell Biochem. 1995; 151: 113-119
- Time course study of oxidative stress in aorta and heart of diabetic rat.Clin Sci. 1996; 91: 441-448
- Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes.Clin Sci. 1998; 94: 623-632
- Partial protection against streptozotocin induced hyperglycemia by superoxide dismutase linked to polyethylene glycol.Acta Endocrinol. 1984; 107: 390-394
- The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat.Free Radic Biol Med. 1995; 18: 833-840
- Oxidative stress and insulin action: is there a relationship?.Diabetologia. 1996; 39: 357-363
- The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes.Free Radic Biol Med. 1996; 21: 719-726
- Lipid peroxide level in plasma of diabetic patients.Biochem Med. 1981; 25: 373-378
- Antioxidant status and lipid peroxidation in type II diabetes with and without complications.Clin Sci. 1996; 90: 255-260
- Metabolic control may influence the increased superoxide generation in diabetic serum.Diabet Med. 1991; 8: 540-542
- Autoantibodies against oxidatively modified low-density lipoproteins in NIDDM.Diabetes. 1995; 44: 60-66
- RRR-a-tocopheryl acetate supplementation at pharmacological doses decreases low density lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus.Am J Clin Nutr. 1996; 63: 753-759
- Dietary and pharmacologic regimens to reduce lipid peroxidation in NIDDM.Am J Clin Nutr. 1995; 62: 1483-1493
- Biology of disease: free radicals and tissue injury.Lab Invest. 1982; 47: 412-426
- Process for extracting lignans from flaxseed.(US patent no 5705618)Jan 1998
- Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside (SDG) isolated from flaxseed.Circulation. 1999; 99: 1355-1362
- Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flaxseed.Mol Cell Biochem. 1997; 168: 117-123
- Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism.Mol Cell Biochem. 2000; 206: 141-150
- Oxidative stress as a mechanism of diabetes in diabetic prone BB rats: effect of secoisolariciresinol diglucoside (SDG).Mol Cell Biochem. 2000; 209: 89-96
- The Zucker diabetic fatty (ZDF) rat.in: Lessons from animal diabetes. Smith-Gordon, London1994: 225-230
- Effect of dietary fat on the development of non-insulin dependent diabetes mellitus in obese Zucker diabetic fatty male and female rats.Atherosclerosis. 2000; 148: 231-241
- Impact of dietary protein and fat source on the development of insulin-dependent diabetes mellitus in the BB rat.Diabetes Res. 1992; 20: 33-41
- Prevention of adoptive transfer in BB rats by prophylactic insulin treatment.Diabetes. 1992; 41: 1273-1277
- Role of oxyradicals in cardiovascular depression and cellular injury in hemorrhagic shock and re-infusion: effect of SOD and catalase.Circ Shock. 1994; 43: 79-94
- Quantitative determination of serum triglycerides by the use of enzymes.Clin Chem. 1973; 19: 476-482
- Enzymatic determination of total serum cholesterol.Clin Chem. 1974; 20: 470-475
- Interlaboratory standardization of glycated hemoglobin determinations.Clin Chem. 1986; 32: 358-360
- Vitamin E supplementation reduces the incidence of diabetes but not insulitis in NOD mice.J Lab Clin Med. 1992; 119: 503-507
- Preventive and therapeutic effects of large–dose nicotinamide injections on diabetes associated with insulitis: an observation in nonobese diabetic (NOD) mice.Diabetes. 1982; 31: 749-753
- Is type II diabetes mellitus a disease of the innate immune system?.Diabetologia. 1998; 41: 1241-1248
- NIDDM as a disease of the innate immune system: association of acute phase reactant and interleukin-6 with metabolic syndrome X.Diabetologia. 1997; 40: 1286-1292
- Elevated serum tumor necrosis factor-alpha levels can contribute to the insulin resistance in type II (non-insulin-dependent) diabetes and in obesity.Diabetologia. 1998; 41: 860-862
- Role of cytokines in inducing hyperlipidemia.Diabetes. 1992; 41: 97-101
- Endocrine effects of cytokines.Oncology. 1994; 8: 43-46
- Secretion of toxic oxygen products by macrophages: regulatory cytokines and their effects on the oxidase.Ciba Foundation Symposium. 1986; 118: 211-230
- Role of cytokines and platelet activating factor in microvascular injury.Int Arch Allergy Appl Immunol. 1989; 88: 88-100
- Neutrophil oxygen radical generation: synergistic responses to tumor necrosis factor and mono/polyunsaturated fatty acids.J Clin Invest. 1996; 97: 1605-1609
- The oxidative metabolism of glutamine: a modulator of reactive oxygen intermediate-mediated cytotoxicity of tumor necrosis factor in L929.J Biol Chem. 1996; 271: 192-196
- Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM.Diabetologia. 1996; 39: 60-69
- Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose.Diabetes. 1990; 39: 420-424
- Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus.Metabolism. 1989; 38: 753-758
- The diabetic Zucker fatty rat (41611).Proc Soc Exp Biol Med. 1983; 173: 68-75
- Ascorbic acid metabolism and the polyol pathway in diabetes.Diabetes. 1989; 38: 257-261
- Restoration of the prostacyclin/thromboxane A2 balance in the diabetic rat: influence of vitamin E.Diabetes. 1982; 31: 947-951
- Glycation and inactivation of human Cu, Zn-superoxide dismutase.J Biol Chem. 1987; 262: 16969-16972
- Magnesium, potassium and zinc deficiency in subjects with type II diabetes.Acta Med Scand. 1988; 224: 461-465
- Dose-dependent production of mammalian lignans in rats and in vitro from purified precursor secoisolariciresinol diglucoside in flaxseed.J Nutr. 1996; 126: 2012-2019
- Chronic exposure to secoisolariciresinol diglucoside alters lignan disposition in rats.J Nutr. 1998; 128: 615-623
- Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, enterodiol and enterolactone.Intl J Angiol. 2000; 9: 220-225
Article info
Publication history
Accepted:
March 14,
2001
Received in revised form:
March 6,
2001
Received:
September 5,
2000
Footnotes
☆Supported by a grant from the Saskatchewan Flax Development Commission and Canadian Adaptation and Rural Development in Saskatchewan.
☆☆Reprint requests: K. Prasad, MD, PhD, FRCP(C), FACC, FICA, Professor Emeritus, Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Rd, Saskatoon, SK Canada, S7N 5E5.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
