secoisolariciresinol-diglucoside and Diabetes-Mellitus--Type-2

There is increased risk of colon cancer in both men and women having diabetes. The objective of the study was to evaluate the role of Secoisolariciresinol diglucoside rich extract(SRE) of L.usissatisimum(flaxseed) in colon cancer associated with type 2 diabetes mellitus.. Diabetes was induced by administering high fat diet with low dose streptozotocin model. After 6 weeks, diabetes was confirmed and 1,2 dimethylhydrazine(25mg/kg, sc) weekly administration was from 6th to 18th weeks. Rats were treated with the SRE(500mg/kg) orally from 6th to 24th week. After 24 weeks, various biochemical and enzymatic parameters were estimated. Animals were sacrificed and colon tissue was separated and subjected to analysis of histopathological, PCNA studies and mRNA expression of CDK4.. Disease control rats depicted hyperglycaemia, hyperinsulinaemia, elevated pro-inflammatory cytokines and cancer biomarker levels, and marked presence of proliferating cells. Treatment with SRE controlled hyperglycaemia, hyperinsulinaemia, reduced pro-inflammatory cytokines and cancer biomarker levels, and decreased no. of proliferating cells. We found that disease control rats depicted over expression of CDK4 mRNA levels which were reduced by SRE treatment.. SRE of L. usitatissimum exhibited chemopreventive effect in colon cancer associated with type 2 diabetes mellitus which might be mediated through inhibition of CDK4.

Topics: Animals; Biomarkers, Tumor; Butylene Glycols; Cell Proliferation; Colonic Neoplasms; Cyclin-Dependent Kinase 4; Cytokines; Diabetes Mellitus, Type 2; Female; Flax; Gene Expression Regulation, Neoplastic; Glucose Tolerance Test; Glucosides; Hyperglycemia; Inflammation Mediators; Male; Phytochemicals; Plant Extracts; Proliferating Cell Nuclear Antigen; Rats, Sprague-Dawley; RNA, Messenger

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 A(1C) (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.

Topics: Animals; Antioxidants; Blood Glucose; Butylene Glycols; Cholesterol; Diabetes Mellitus, Type 2; Disease Models, Animal; Female; Flax; Glucosides; Glycated Hemoglobin; Malondialdehyde; Oxidative Stress; Rats; Rats, Zucker; Triglycerides