Food Chemistry 158 (2014) 429–432

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Short communication

Effects of soybean oligosaccharides on antioxidant enzyme activities and insulin resistance in pregnant women with gestational diabetes mellitus Bei-bei Fei a, Li Ling a,⇑, Chen Hua b, Shu-yan Ren c a b c

Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China Department of Emergency, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China Clinic of Nutrition, Suzhou Municipal Hospital, Suzhou 215002, China

a r t i c l e

i n f o

Article history: Received 26 April 2012 Received in revised form 3 February 2014 Accepted 19 February 2014 Available online 6 March 2014 Keywords: Soybean oligosaccharides Gestational diabetes mellitus Antioxidant enzyme Insulin resistance

a b s t r a c t The effects of soybean oligosaccharides (SBOS) on antioxidant enzyme activities and insulin resistance in pregnant women with gestational diabetes mellitus (GDM) were investigated. Ninety-seven pregnant women with GDM were randomly divided into two groups, the control group (51 cases) and the SBOS group (46 cases). Before the group separation, the blood sugar level in patients was maintained stable by regular diet and insulin treatment. The control group was continued with the insulin treatment, while the SBOS group was treated with the combination of insulin and SBOS. Results showed that SBOS were able to reduce oxidative stress and alleviate insulin resistance in pregnant women with GDM, which indicates that SBOS may play an important role in the control of GDM complications. Ó 2014 Elsevier Ltd. All rights reserved.

1. Introduction Gestational diabetes mellitus (GDM) is a special type of diabetes often associated with pregnancy (Bellamy, Casas, Hingorani, & Williams, 2009; Matuszek, Lenart-Lipin´ska, Burska, Paszkowski, & Smolen´ ANowakowski, 2011). GDM imposes high risks on pregnancy and induces a series of symptoms including macrosmia, fetal abnormalities, high blood pressure, and polyhydramnios (Matuszek et al., 2011). In infants born by GDM mother, neonatal respiratory disease syndrome, hypocalcemia and hypoglycemia may occur after birth, and the perinatal mortality rate is high among these infants. Meanwhile, women with GDM, as well as their children, are more prone to other health problems such as type 2 diabetes (Löbner et al., 2006; Nelson, Matthews, & Poston, 2010). However, it is controversial to use current oral hypoglycemic drugs in pregnant women because of the safety and effectiveness concerns. Many diabetes-related organizations, including

Abbreviations: SBOS, soybean oligosaccharides; GDM, gestational diabetes mellitus; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; TBARS, thiobarbituric acid reactive substance; MDA, Malondialdehyde; FPG, fasting plasma glucose; FINS, fasting insulin; APN, adiponectin; HOMA-IR, insulin resistance index; HBCI, islet bcells function index. ⇑ Corresponding author. Tel./fax: +86 0512 68282030. E-mail address: [email protected] (L. Ling). http://dx.doi.org/10.1016/j.foodchem.2014.02.106 0308-8146/Ó 2014 Elsevier Ltd. All rights reserved.

American Diabetes Association, are cautious about using these drugs in pregnant women. As a result, the clinical application of these drugs in pregnant women is limited (American Diabetes Association, 2013). Therefore, it is of great interest to develop other effective treatments, especially those that can be safely used in pregnant women (Bellamy et al., 2009; Löbner et al., 2006). Soybean oligosaccharides (SBOS), which are isolated from the soybean seeds, are ‘‘potential prebiotic material’’ and approved by the Food and Drug Administration as GRAS (Generally Recognized As Safe) ingredient in USA. (Chen, Jun, Jun, Bo, & Rui, 2010a; Kim, Kim, & Hwang, 2003; Zhou, Kong, Yang, & Yin, 2012). Soybean oligosaccharides (SBOS) is a general claim of soluble oligosaccharides contained in soy or other legume. SBOS consist most of raffinose, stachyose and sucrose. Sucrose is formed by combination of a-D-glucose and b-D-fructose through a-1,2 glycosidic bond. Raffinose is a trisaccharide containing galactose linked a-(1–6) to the glucose unit of sucrose. Stachyose is a tetrasaccharide containing a galactose linked a-(1–6) to the terminal galactose unit of raffinose. Other reported major sugar of soybeans is sucrose with lower amounts of the monosaccharides, fructose, rhamnose and arabinose; significant levels of glucose occurred only in immature seeds. (Chen, Jun, Jun, Bo, & Rui, 2010a; Chen, Jun, Jun, Bo, & Rui, 2010b; Kim et al., 2003). SBOS have been shown to be a promising candidate for the prevention of many

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chronic diseases such as cancer, osteoporosis, atherosclerosis and menopausal disorders (Chen et al., 2010b; Espinosa-Martosy & Rupérez, 2006; Mateos-Aparicio, Redondo-Cuenca, VillanuevaSuárez, & Zapata-Revilla, 2008). It has been reported that SBOS treatment reduces oxidative stress and abnormal blood lipid levels induced by high fat diets (Chen et al., 2010b). However, the effect of SBOS on antioxidant enzyme activities and insulin resistance in pregnant women with GDM remains not clear. In this report, we studied 97 patients that were diagnosed as GDM according to the National Diabetes Data group (NDDG) standard. The effects of SBOS on antioxidant enzyme activities and insulin resistance in pregnant women with GDM were investigated. 2. Materials and methods 2.1. Materials SBOS (SBOS consist most of raffinose, stachyose and sucrose, and the proportion of raffinose and stachyose is above 60%) were purchased from One Hundred Love Technology Co., Ltd. (Harbin, China). NovoRapid (Insulin Aspart Injection) and Novolin N (isophane protamine biosynthetic human insulin) were purchased from Novo Nordisk Company (Copenhagen, Denmark). Fasting plasma glucose (FPG) kit was provided by DiaSys Diagnostic Systems (Holzheim, Germany). Fasting insulin (FINS) kit was from Beijing Furui Biological Engineering Company (Beijing, China). Adiponectin (APN) ELISA kit was obtained from AssayPro (St. Charles, USA). Superoxide dismutase (SOD) detection kit, Glutathione peroxidase (GPx) detection kit, Catalase (CAT) detection kit and Malondialdehyde (MDA) detection kit were obtained from Nanjing Jiancheng Bioengineering Institute (Nanjing, China). 2.2. Patients and study design Between June 2007 and March 2009, 97 pregnant women diagnosed as GDM according to the National Diabetes Data group (NDDG) standard were recruited in this study at Suzhou Municipal Hospital (Suzhou, China). The inclusion criterion was that pregnant women are older than 20 and carry singleton fetus, excluding those with diabetes, kidney disease, liver disease, hypertensive disease and intrahepatic cholestasis during pregnancy. Signed forms of consent were obtained from all participants, and the study was approved by Suzhou Municipal Hospital Research Ethics Board. These 97 pregnant women whose blood sugar level was maintained stable by regular diet and insulin treatment were randomly divided into two groups. The control group (51 cases) and the SBOS group (46 cases). The differences in age, weight before pregnancy, body mass index (BMI), height and family history of diabetes in first-degree relatives between the two groups were not statistically significant. The control group was continued with the treatment by insulin alone through subcutaneous injection of a short-term effect insulin NovoRapid before every meal (three times a day), and an intermediate-term effect insulin Novolin N before sleep. The SBOS group was treated with the combination of the insulin (as in the control group) and SBOS (10 g/day in 200–300 ml warm water, took in orally before sleep). In the first 7d of treatment, during which insulin dose adjustment was needed, the blood glucose level was monitored seven times a day (one time each before lunch and dinner, one time each 2 h after the three meals, one time in the morning when the stomach is empty, one time at 0:00 in the morning). The blood glucose level was checked and recorded three to four times a day after it maintained stable, and the dose of insulin was adjusted according to the blood glucose level. The control standard levels of blood glucose are: 4.4–6.7 mmol/L at 0:00 in the morning,

3.3–5.6 mmol/L in the morning when the stomach is empty, 3.3–5.8 mmol/L before lunch and dinner, 4.4–6.7 mmol/L 2 h after the three meals. 2.3. Biochemical analysis methods 2.3.1. Plasma glucose, insulin and APN analysis Before treatment and after treatment for 8 weeks, fasting venous blood (10 ml) was withdrawn. The venous blood was divided into two aliquots: one aliquot (5 ml) was used to measure the FPG and FINS, and the other (5 ml) was centrifuged at 3000 rpm for 15 min to collect serum. The serum was stored at 80 °C for later use. Serum FPG, FINS and APN levels were measured according to the manufacturer’s instructions. 2.3.2. Antioxidant enzyme activity analysis The serum SOD activity was assayed by the inhibition of xanthine/xanthine oxidase-mediated reduction of cytochrome c as previously described (Sheng, Gu, & Xie, 2013). One unit of SOD activity was defined as the amount of enzyme required to produce 50% inhibition in the calibration curve obtained with standard SOD, and was expressed as U/mg protein. The GPx activity was determined using the method previously reported (Sheng, Gu, Xie, Zhou, & Guo, 2007). One unit of enzyme activity was defined as the amount of NADPH (in nmol) consumed per min per mg protein. CAT activity was assayed by the method described by Wu et al. (2008). The enzyme-catalyzed conversion of H2O2 was measured. In brief, an aliquot of 0.5 ml cold sample, or a blank consisting of 0.5 ml distilled water was added in test tubes. The enzymatic reaction was initiated by adding 5 ml of cold 6 mM H2O2. After 3 min the reaction was stopped by adding 1 ml of 3 M H2SO4. Then 7 ml of 0.01 M KMnO4 was added, and the absorbance was measured at 480 nm within 30–60 s. The concentration of TBARS was measured by a method reported by Sheng et al. (2013) with modifications. The TBARS concentration was expressed as MDA equivalents. 2.3.3. Insulin resistance analysis The insulin resistance index (HOMA-IR) and islet bcells function index (HBCI) were calculated with a homeostasis model assessment method (HOMA) using the following formula (Chen et al., 2005):

HOMA-IR ¼ FINS  FPG=22:5 HBCI ¼ FINS  20=ðFBG-3:5Þ

2.4. Statistical analysis Statistical analysis was performed using SPSS software version 11.5 (SPSS Institute, Chicago, IL, USA). All data were expressed as means ± SEM. Student t test was used to assess the statistical significance. P < 0.05 was considered statistically significant.

3. Results 3.1. Effects of SBOS on serum SOD, CAT, GPx activities and TBARS level As shown in Table 1, the serum SOD, CAT and GPx activities in the SBOS group were significantly higher than those in the control group (P < 0.01), while the TBARS level in the SBOS group was significantly lower than that in the control group (P < 0.01).

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B.-b. Fei et al. / Food Chemistry 158 (2014) 429–432 Table 1 Effects of SBOS on serum SOD, CAT, GPx activities and TBARS level. Group

Cases

SOD (U/ml)

CAT (U/ml)

GPx (U/ml)

TBARS (nmol/ml)

Control group SBOS group

51 46

86.54 ± 5.42 105.51 ± 11.52a

58.85 ± 2.07 85.86 ± 1.82a

166.06 ± 4.96 201.57 ± 2.39a

8.04 ± 1.39 5.26 ± 0.91a

All data were expressed as means ± SEM. SBOS: soybean oligosaccharides; SOD: superoxide dismutase; CAT: catalase; GPx: glutathione peroxidase; TBARS: thiobarbituric acid reactive substances. a P < 0.01, compared with control group.

Table 2 Effects of SBOS on FPG, FINS, APN, HOMA-IR and HBCI levels. Group

Cases

FPG (mmol/L)

FINS (mU/L)

APN (mg/L)

HOMA-IR

HBCI

Control group SBOS group

51 46

5.05 ± 0.62 4.58 ± 0.59a

11.33 ± 4.35 9.30 ± 2.38b

5.61 ± 1.09 10.87 ± 1.11b

1.72 ± 0.52 1.46 ± 0.38b

222 ± 13 187 ± 21b

All data were expressed as means ± SEM. SBOS: soybean oligosaccharides; FPG: fasting plasma glucose; FINS: fasting insulin; APN: adiponectin; HOMA-IR: insulin resistance index; HBCI: islet bcells function index. a P > 0.05, compared with control group. b P < 0.01, compared with control group.

3.2. Effects of SBOS on serum FPG, FINS, APN, HOMA-IR and HBCI levels As shown in Table 2, the FINS and HOMA-IR levels in the SBOS group were significantly lower (P < 0.01), whereas APN level in the SBOS group was significantly higher (P < 0.01) compared to those in the control group. The FPG and HBCI levels in the SBOS group appeared to be lower than those in the control group, but the difference was not significant (P > 0.05). 3.3. Effects of SBOS on insulin treatment time and dosage As shown in Table 3, the average time and the total time of insulin treatment in the SBOS group appeared to be longer than those in the control group, but the difference was not significant (P > 0.05). In contrast the total insulin dosage in the SBOS group was lower than that in the control group (P < 0.01). 4. Discussion The incidence rate of GDM is increasing and endangering the health of maternal and children in recent years, the precise mechanism of it is still unknown. Recently, it is considered as a symptom of multiple pathogenic factors rather than just one simple factor. Insulin resistance plays a key role in the development of GDM, and is also the main pathological feature of GDM. It was closely combined with the declining antioxidant activity and increasing reactive oxygen species (ROS). Oxidative stress can stimulate insulin resistance through the activation of Serine/ threonine protein kinase. Lipid peroxide (LPO) is the effective product of ROS with unsaturated fatty acids, and reflects the metabolism rate of free radical, which may result in cell damage and disturb normal metabolic activity. Maleic dialdehyde (MDA) is a hydrolysis product of this process, and can be clinically detected and reflects the rate and strength of the body lipid peroxidation. Antioxidant enzymes are capable of scavenging ROS and lipid peroxidation products, thereby protecting cells and tissues from oxidative damage. To prevent oxidative stress, a balance between antioxidants and ROS needs to be kept. When the balance is disrupted, ROS may accumulate and trigger oxidative injury through lipid peroxidation and protein oxidation, and stimulate toxic product synthesis and cell death (Edeas, 2009; Fang, Seki, & Maeda, 2009; Keir, Dewhirst, Kirkpatrick, Bigner, & BatinicHaberle, 2011). SOD converts superoxide radicals to molecular oxygen and H2O2, and CAT decomposes H2O2 to molecular oxygen

Table 3 Effect of SBOS on the dosage of insulin. Group

Cases

Average weeks

Total weeks

Insulin dose (U)

Control group SBOS group

51 46

8.84 ± 1.08 9.04 ± 1.21

420 451

34.82 ± 6.71 24.35 ± 3.48a

All data were expressed as means ± SEM. SBOS: soybean oligosaccharides. a P < 0.01, compared with control group.

and water (Fang et al., 2009). A variety of evidences indicate that antioxidant enzyme activities are lower in diabetes patients, which in turn exacerbates existing oxidative stress (Afolayan & Sunmonu, 2011; Suhail, Patil, Khan, & Siddiqui, 2010). APN is an adipose tissue-derived protein, which can reduce insulin sensitivity and decrease glucose utilisation, low serum APN level is correlated with declining insulin sensitivity and increasing insulin resistance. In this work, we demonstrated that oxidative stress occurred in pregnant women with GDM as evidenced by elevated levels of MDA and decreased levels of antioxidant enzymes including CAT, SOD and GPx in the serum. These changes suggest increased level of lipid peroxidation and oxidative stress. The activities of antioxidant enzymes were significantly higher when SBOS was administered to pregnant women with GDM. In addition, we found that SBOS treatment for 8 weeks could improve FPG, FINS and APN levels in pregnant women with GDM, compared to the control group, the insulin resistance was alleviated and the total insulin dosage was reduced. This study showed SBOS together with insulin can increase the activity of antioxidant enzymes and reduce the MDA level, as well as improve insulin resistance and serum APN level in pregnant women with GDM. People more and more pay attention to the antioxidant activity of SBOS. Huang et al.(2006) reported that the activities of antioxidant enzymes in liver such as CAT, SOD, and GPx were significantly elevated when SBOS was administered to rats orally once per day for 6 weeks. Chen et al. (2010b) showed that SBOS can dose-dependently reduce oxidative stress and improve abnormal blood lipid levels in the SBOS-treated rats. Our study showed SBOS can increase the activity of antioxidant enzymes and alleviate insulin resistance in pregnant women with GDM. But, the antioxidant mechanism of SBOS is still not clear, still need further study. Chen et al. (2010b) reported that one of the possible mechanisms was polyphenolic-associated polysaccharide (formation of nonextractable complex between high molecular weight phenolics and polysaccharides). Those kinds of phenolic

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compounds showed antioxidant activity due to their redox properties, which play an important role in absorbing and neutralising free radicals, quenching singlet and triple oxygen or decomposing peroxide. Zhou et al. (2012) reported that a relatively low molecular weight and a relatively high uronic acid content appeared to increase the antioxidant activity, the mechanism was still not clear now. So, further structural studies were needed to explore the mechanism. In summary, we provided evidence that SBOS could alleviate insulin resistance in pregnant women with GDM by enhancing antioxidant enzyme activities. These findings indicate that the anti-oxidative property of SBOS could be a potential mechanism for its anti-diabetes effects and provide support for its application as an anti-diabetes agent. References Afolayan, A. J., & Sunmonu, T. O. (2011). Ameliorates oxidative stress in the pancreas of streptozotocin-induced diabetic wistar rats. Bioscience, Biotechnology, and Biochemistry, 75, 2083–2086. American Diabetes Association. (2013). Standards of medical care in diabetes-2013. Diabetes Care, 36(Suppl. 1), S11–S61. Bellamy, L., Casas, J. P., Hingorani, A. D., & Williams, D. (2009). Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet, 373, 1773–1779. Chen, T. J., Ji, C. Y., Pang, Z. C., Yang, Y. P., Wang, W., Li, H. J., et al. (2005). Heritability analysis of insulin sensitivity and the effect of age and sex: a twin study in Chinese aged 5–18. Beijing Da Xue Xue Bao, 37, 90–93. Chen, H., Jun, L. L., Jun, J. Z., Bo, X., & Rui, L. (2010). Chemical composition analysis of soybean oligosaccharides and its effect on ATPase activities in hyperlipidemic rats. International Journal of Biological Macromolecules, 46, 229–231. Chen, H., Jun, L. L., Jun, J. Z., Bo, X., & Rui, L. (2010). Effect of soybean oligosaccharides on blood lipid, glucose levels and antioxidant enzymes activity in high fat rats. Food Chemistry, 119, 1633–1636. Edeas, M. (2009). Anti-oxidants, controversies and perspectives: How can the failure of clinical studies using anti-oxidants be explained? Journal de la Société de Biologie, 203, 271–280. Espinosa-Martosy, I., & Rupérez, P. (2006). Soybean oligosaccharides. Potential as new ingredients in functional food. Nutrición Hospitalaria, 21, 92–96.

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Effects of soybean oligosaccharides on antioxidant enzyme activities and insulin resistance in pregnant women with gestational diabetes mellitus.

The effects of soybean oligosaccharides (SBOS) on antioxidant enzyme activities and insulin resistance in pregnant women with gestational diabetes mel...
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