الفهرس 
ِAcknowledgementOnly 14 pages are availabe for public view
 |  | from | 294 |  |  |
| | | from | 294 | | |
Abstract
Diabetes mellitus, a chronic metabolic disorder, is one of the most important health problems in the world,especially in developing countries. Type 2 diabetes is rapidly increasing worldwide thereby posing a severe burden on individual and public health. Type 2 diabetes mellitus (T2DM) is characterized by various combinations of β-cell failure and insulin resistance leading to hyperglycemia and glucose intolerance.
The treatment of diabetes with synthetic drugs is generally not preferred because of its high cost and the range of side effects caused. Efforts are therefore required on many fronts to address this major public health problem. Hence, the search for a safe and effective drug which can reduce the many harmful effects of T2DM, including hyperglycemia, hyperlipidemia, oxidative stress, inflammation, and arthrosclerosis, among others, is thus urgently needed. Currently, there is much interest in the usefulness of citrus fruits because of their intake appears to be associated with reduced risk of certain chronic diseases and increased survival.
Key words:
Streptozotocin, diabetes mellitus, hesperidin, naringin, oxidative stress, insulin resistance.
Aim of work:
The present study was designed to evaluate the efficacy of the citrus flavonoids, hesperidin and naringin, on the impaired glucose tolerance, insulin resistance and hyperlipidemia in high-fat diet/streptozotocin induced-diabetic albino rats and to suggest their probable mechanisms of action.
Materials and methods:
Male albino rats were divided into four groups. Group 1 was normal control, and others were induced with diabetes by feeding a high fat diet for 2 weeks followed by an intraperitoneal injection of streptozotocin (35 mg/kg b.wt.). Group 2 was kept as diabetic control, and groups 3 and 4 were further treated with an oral dose of 50 mg/kg hesperidin and naringin for 4 weeks. By the end of the experimental period rats were sacrificed, blood samples were taken and serum was isolated for estimation of glucose, insulin, TNF-α, IL-1β, IL-6, lipid profile, adiponectin, resistin, pro-inflammatory cytokines, non-enzymatic antioxidants, nitric oxide, malondialdehyde and heart function parameters. In addition, livers were excised for estimation of glycogen content, carbohydrate metabolizing enzymes, antioxidant defense system, malondialdehyde, nitric oxide and HMG-CoA reductase activity. Moreover, visceral adipose tissue was taken for the study of gene expression of PPARγ, TNF-α, adiponectin, resistin and GLUT4 as well as protein expression of GLUT4. Muscles were also taken for glycogen content determination. The in vitro study of insulin release from isolated islets of Langerhans and peripheral glucose uptake were also carried out. An in situ study of the intestinal glucose absorption was also performed.
Results:
The diabetic control group exhibited hyperglycemia, dyslipidemia, insulin resistance, oxidative stress, diminished antioxidant defense system and deteriorated expression of the adipose tissue adipocytokines. Treatment of the diabetic rats with either hesperidin or naringin profoundly alleviated the metabolic deteriorations observed in type 2 diabetic rats.
Conclusion:
The present investigation imparts new information on the improvement effects of hesperidin and naringin in high fat diet low dose streptozotocin-induced type 2 diabetic rats and provides evidence that the protective effects are, possibly, due to decline in oxidants and proinflammatory cytokines production, and regulation of adipose tissue gene expression levels. Further, study suggests that both hesperidin and naringin are effective in ameliorating diabetic complications such as hyperglycemia and oxidative damage. Thus, hesperidin and naringin may be considered as potential candidates in the armamentarium of drugs for treatment in diabetic patients, pending further in vivo and clinical investigations in human beings to trace out their antidiabetic efficacies and their exact mechanistic pathways.