Resistant starch manipulated hyperglycemia/hyperlipidemia and related genes expression in diabetic rats

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Abstract

The effect of resistant starch (RS) administration on biological parameters including blood glucose, lipids composition and oxidative stress of type 2 diabetic rats was investigated. The results showed blood glucose level, total cholesterol and triglycerides concentrations significantly reduced, and high-density lipoprotein cholesterol concentration was doubly increased in the rats of RS administration group compared to model control group (P < 0.01). The analyses of genes involved in glucose and lipid metabolism pathways demonstrated that the expression levels of lipid oxidation gene Acox1, glycogen synthesis genes, GS2 and GYG1, and insulin-induced genes, Insig-1 and Insig-2, were significantly up-regulated (P < 0.01). In contrast, fatty acids and triglycerides synthesis and metabolism-related gene SREBP-1, fatty acid synthesis gene Fads1 and gluconeogenesis gene G6PC1 were greatly down-regulated. The mechanism study shows that the lowering of blood glucose level in diabetic rats by feeding RS is regulated through promoting glycogen synthesis and inhibiting gluconeogenesis, and the increased lipid metabolism is modulated through promoting lipid oxidation and cholesterol homeostasis. Our study revealed for the first time that the regulation of hepatic genes expression involved in glucose and lipids metabolisms in diabetic rats could be achieved even at a moderate level of RS consumption.

Introduction

Diabetes is one of the most costly and burdensome chronic diseases, which gains increasingly public health concern. Diabetes mellitus (DM) affects 8% of the United States and China population and 23% of the population >60 years of age, mostly as type 2 diabetes. Approximately 2% of years of healthy life lost due to death and nonfatal illness or impairment was attributable to diabetes in year 2010 [1]. Due to the complex pathogenesis of DM, the exact mechanism on how those factors cause DM is still unclear. Many studies have suggested that diabetes occurs due to the imbalance between free radical formation and the ability of the organism's natural antioxidants [2], [3]. It is not surprising there is a great interest in novel approaches to DM management. However, despite the increasing number of drugs available for DM treatment, the control of DM has not been improved at the population level. Thus, search for natural health products as an alternative approach to current medications has become many people's interests. It is well documented that resistant starch (RS) administration could improve the glucose intolerance and insulin resistance [4], [5]. However, the mechanisms (especially at the molecular level) by which this takes place are still not fully clear [6]. A recent report demonstrated for the first time that at least part of the beneficial effects of a higher level of RS intake (419 g/kg diet) in the context of a high-fat feeding could be driven by changes elicited at the hepatic level [6]. Similarly, Choi et al. [7] used cooked rice (containing RS type 3) for studying RS physiological property and also found that the cooked rice could prevent hyperlipidemia in hamsters induced by a high-fat/cholesterol diet through the regulation of the expression level of hepatic genes involved in lipids metabolism.

Nevertheless, despite this important body of evidence, the mechanisms by which the RS intake exerts its beneficial effects have not been still completely elucidated, in particular, using different RS consumption level by different metabolic syndrome (MS) models for revealing the evidence of interorgan relationship evidence between the liver and gut-derived small metabolites in the development of MS-related pathophysiology. Thus, this paper aims to study the influence of RS administration at a moderate consumption level on blood glucose level and blood lipids composition in type 2 diabetic rats. Moreover, the regulations of gene expressions related to glucose and lipid metabolisms are also investigated following the RS administration.

Section snippets

Materials

RS, from high amylose maize (Hi-maize™), was obtained from National Starch and Chemical Company, NSW, Australia. Streptozotocin (STZ) was purchased from Sigma-Aldrich (St. Louis, MO, USA). Other chemicals were of reagent grade and used as-received.

Animals and diets

Healthy male Sprague–Dawley rats (SD, non-diabetic) of ∼190 ± 10 g weight were purchased from the animal house, Chinese Military Medical Science Academy. Twenty-four rats were divided into three groups randomly: normal control, model control and RS

Effects of RS administration on body gain in diabetic rats

The initial weight of the rats had no significant difference among the three groups (P > 0.05) (Table 2), indicating the random grouping was reasonable. The body mass of the rats in normal control group gradually increased following the 4-week's experiment, suggesting the dietary composition designed was appropriate. Following the injection of STZ, the rats in the two diabetic groups (i.e. model control group and RS administration group) displayed a depression of body gain, at which the weight of

Discussion

It has been established that the consumption of food with a higher RS content resulted in a lower postprandial glucose concentration compared with the foods containing higher digestive carbohydrates in human studies [10], [11], [12] and type 2 diabetic animal model [13]. However, the molecular basis of such effects remains to be elucidated. Thus, in this study, the measurement of the related genes of glucose metabolism, including the rate limiting enzymes of glycogenesis, GS and GYG1, found

Conclusion

The present study brings new evidences that the existence of RS in the diet increases a cascade of metabolic adaptations and RS brings both functions of the increase in lipid oxidation and the concomitant reduction in glucose availability. Taken together, our results demonstrated that RS consumption even at a moderate level (about 8% of the total diet) could still attenuate the metabolic disorders of glucose and lipid in diabetic rats, improve insulin sensitivity or reduce insulin resistance,

Acknowledgements

This work was financially supported by the National Nature Science Foundation of China (No. 31471701), the China-European Research Collaboration Program (SQ2013ZOA100001) and 2015 Tianjin Research Program of Application Foundation and Advanced Technology.

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