Open Access, Peer-reviewed
pISSN 1976-1457
eISSN 2005-6168
    Nutr Res Pract. 2008 Winter;2(4):252-258. English.
    Published online Dec 30, 2008.
    https://doi.org/10.4162/nrp.2008.2.4.252
    ©2008 The Korean Nutrition Society and The Korean Society of Community Nutrition
    Original Article

    Effect of fructose or sucrose feeding with different levels on oral glucose tolerance test in normal and type 2 diabetic rats

    Sanghee Kwon, You Jin Kim and Mi Kyung Kim
      • Department of Food and Nutritional Sciences, Ewha Womans University, 11-1 Daehyung-dong, Seodaemun-gu, Seoul 120-750, Korea.
    • Corresponding Author: Mi Kyung Kim, Tel. 82-2-3277-3092, Fax. 82-2-3277-2862, Email: mkk@ewha.ac.kr
    Received July 16, 2008; Revised November 24, 2008; Accepted December 08, 2008.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    This study was designed to determine whether acute fructose or sucrose administration at different levels (0.05 g/kg, 0.1 g/kg or 0.4 g/kg body weight) might affect oral glucose tolerance test (OGTT) in normal and type 2 diabetic rats. In OGTT, there were no significant differences in glucose responses between acute fructose- and sucrose-administered groups. However, in normal rats, the AUCs of the blood glucose response for the fructose-administered groups tended to be lower than those of the control and sucrose-administered groups. The AUCs of the lower levels fructoseor sucrose-administered groups tended to be smaller than those of higher levels fructose- or sucrose-administered groups. In type 2 diabetic rats, only the AUC of the lowest level of fructose-administered (0.05 g/kg body weight) group was slightly smaller than that of the control group. The AUCs of fructose-administered groups tended to be smaller than those of the sucrose-administered groups, and the AUCs of lower levels fructose-administered groups tended to be smaller than those fed higher levels of fructose. We concluded from this experiment that fructose has tendency to be more effective in blood glucose regulation than sucrose, and moreover, that smaller amount of fructose is preferred to larger amount. Specifically, our experiments indicated that the fructose level of 0.05 g/kg body weight as dietary supplement was the most effective amount for blood glucose regulation from the pool of 0.05 g/kg, 0.1 g/kg and 0.4 g/kg body weights. Therefore, our results suggest the use of fructose as the substitute sweetener for sucrose, which may be beneficial for blood glucose regulation.

    Keywords
    Fructose; sucrose; oral glucose tolerance test

    Introduction

    The dietary habit of Koreans has changed progressively to one that resembles that of people in the Western world (The Korean Nutrition Society, 2006) and this has caused an increase in the consumption of sucrose. According to the food balance sheet provided by the "Korean Rural Economic Institute" (2004), the average amount of sucrose supplied for each Korean adult was 4.8 g per day in 1962 and has increased to 57 g per day in 2004. Although it is still relatively small compared with that of the USA, the production and consumption are still increasing (The Korean Nutrition Society, 2006). Type 2 diabetes is increasing at epidemic rates in the USA (Mokdad et al., 1999; Mokdad et al., 2000; Mokdad et al., 2001) and in the developing countries including China (Pan et al., 1997) and India (Ramachandran et al., 1997). From 1935 to 1996, the prevalence of diagnosed type 2 diabetes climbed nearly 765% (Centers for Disease Control and Prevention NCfHS, Division of Health Interview Statistics, 1997). The global figures are predicted to rise 46% from 150 million cases in 2000 to 221 million in 2010 (Zimmet et al., 2001). The incidence of type 2 diabetes is also at an epidemic level in Korea and is increasing. For example, the incidence of diabetes for those aged 30 years or older has increased from 6.6% in 1998 to 8.1% in 2005 (Ministry of Health and Welfare, 1999; Ministry of Health and Welfare, 2006). Epidemiological studies have identified a significant positive correlation between dietary sucrose intake and the incidence of diabetes (Basciano et al., 2005). We suspect that this steady increase in sucrose consumption in Korea will contribute to the increase of diabetes (Basciano et al., 2005), so there is an urgent need for the selection and application of appropriate substitute sweeteners.

    Fructose is believed to be more slowly absorbed from the gastrointestinal tract than glucose. When disaccharides such as sucrose or maltose enter the intestine, they are cleaved by disaccharidases. A sodium-glucose cotransporter absorbs glucose that is formed from the cleavage of sucrose. In contrast, fructose has no active absorption mechanism in the intestinal mucosa but is slowly and incompletely absorbed by facilitated diffusion (Bray et al., 2004; Uusitupa, 1994). Because of this slow absorption, the blood glucose-increasing effect of fructose is lower than after ingestion of most other carbohydrate sources (Bantle et al., 1983; Cannon et al., 1986; Crapo & Kolterman, 1984; Henry et al., 1991; Jeckins et al., 1981; Swan et al., 1966). After absorption, glucose and fructose enter the portal circulation and are transported to the liver, where fructose can be taken up and converted to glucose, or pass into the general circulation (Bray et al., 2004). Fructose is metabolized mainly by the liver and to a lesser extent by the kidney and intestinal mucosa (Ludwig et al., 1999; Truswell, 1992). Fructose transepithelial transport in intestine is initiated at the apical side by GLUT 5 and GLUT 2, and is thought to be released through the basolateral membrane by GLUT 2 (Kellett & Brot-Laroche, 2005). In the metabolism of fructose, the first reaction is catalyzed by fructokinase, an enzyme that is not dependent on insulin. Fructose does not stimulate insulin secretion from pancreatic β cells. The lack of stimulation by fructose is likely because of the low concentrations of the fructose transporter GLUT5 in β cells (Basciano et al., 2005; Bray et al., 2004; Curry, 1983; Mayer, 1993; Sato et al., 1996; Uusitupa, 1994). In contrast to sucrose and glucose, some nutritionists regard fructose as a relatively safe form of sugar. Because it does not require insulin for uptake into cells, moderate fructose intake does not affect blood glucose levels adversely, at least in the short term (Bantle et al., 1986). Glycemic index (GI) is a system of classifying carbohydratecontaining foods according to how fast they are digested and absorbed during the postprandial period. The GI has a value of 100 for glucose and baked potato, 19 for fructose and 68 for sucrose (Truswell, 1992). A related concept, glycemic load (GL), also takes into consideration the amount of carbohydrates in portion of food (Ciok & Dolna, 2006). Glycemic Index (GI) and Glycemic Load (GL) play a pivotal role in carbohydrate classification and for food choice by diabetic patients. Postprandial glycemic response and insulinemia are strongly related to the values of GI and GL (Pankowska et al., 2006). Several recent studies have suggested that consuming low GI and GL diet may be associated with a lower risk for type 2 diabetes (Salmeron et al., 1997a; 1997b; 1997c). In addition, fructose is sweeter than sucrose. In sweetness comparative studies, when sucrose is set at a scale of 100, fructose is 173 and glucose is 74 (Schauberger, 1977). For these reasons, it has been proposed as a useful energy source and a substitute for sucrose in the diet for patients with diabetes (Bantle, 1989; Koivisto, 1978; Nutrition Subcommittee of the British Diabetic Association's Professional Advisory Committee, 1990; Olefsky & Crapo, 1980). However, diets specifically high in fructose have been shown to contribute to metabolic disturbances in animal models resulting in weight gain, hyperlipidemia and hypertension (Hwang et al., 1987; Kasim-Karakas et al., 1996).

    Some studies examining the effects of fructose consumption on blood glucose regulation have shown conflicting results (Jurgens et al., 2005). The optimal dose of fructose compared with sucrose has not been well evaluated. The metabolic consequence of fructose, compared with sucrose, needs to be examined in experimental animals and human with normal or type 2 diabetes (Olefsky & Crapo, 1980). Therefore, this study was designed to determine whether the supplement of different levels of fructose or sucrose might affect blood glucose regulation in Sprague-Dawley (SD) and Goto-Kakizaki (GK) rats with type 2 diabetes, respectively. The goal was to determine the effect of fructose, compared with sucrose, on glucose tolerance, as dietary supplements.

    Materials and Methods

    Animals and Diets

    Seventy male SD rats of nine-month old [Slc (SD), Outbred, Charles River Origin, Japan SLC, Inc] were placed in individual stainless steel wire-mesh cages in a room with 12:12 h light-dark cycle, temperature of 22-24℃ and a relative humidity of 45 ± 5%. The rats were fed with a normal diet for the first seven days of adaptation. The diet was formulated according to the nutrient content of the 93M diet of the American Institute of Nutrition (AIN) (Portha et al., 1991). Cornstarch (Dyets Inc., USA) was included as a source of carbohydrate, soybean oil (CJ Co., Korea) was included as a source of lipid and casein (Dyets Inc., USA) was included as a source of protein. Mineral and vitamin mixtures, prepared in accordance with the 1993 recommendation of the AIN, were purchased from Dyets, Inc., USA. SD rats weighed 632 ± 15 g at the end of the adaptation period. They were then stratified according to body weight and allocated randomly into seven groups for the experimental period.

    Seventy male GK rats of six-week old [GK/Slc, Inbred, Tohoku University School of Medicine, Japan SLC, Inc] were placed in individual stainless steel wire-mesh cages in a room with 12:12 hr light-dark cycle, temperature of 22-24℃ and relative humidity of 45 ± 5%. The rats were fed with a normal diet for the first seven days of the adaptation period. The diets of GK rats were formulated according to the nutrient content of the 93G diet of the AIN (Portha et al., 1991). The GK rat is a spontaneous diabetic animal model of non-insulin-dependent diabetes mellitus, which is characterized by progressive loss of β-cells in the pancreatic islets with fibrosis. This model was produced by repeated selective breeding of rats with glucose intolerance starting from a nondiabetic Wistar rat colony. The characteristics of the GK rat include mild hyperglycemia at fasting, impaired glucose tolerance on glucose load and impaired secretion of insulin in response to glucose in vivo (Hasegawa et al., 2001; Koyama et al., 1998; Ostenson et al., 1993; Ostenson, 1996). The GK rats weighed 132 ± 5 g at the end of the adaptation period. The rats were then stratified according to body weight and blocked randomly into seven groups for the experimental period.

    This study was conducted at the nutrition laboratory of Ewha Womans University in compliance with the Guide for the Care and Use of Laboratory Animals (Ostenson et al., 1993). The rats were allowed free access to the experimental diets and deionized water during the experimental period. Body weights were recorded once a week. For determination of food intake, the amount of food offered was weighed and the weights of any orts were recorded three times per week.

    Oral glucose tolerance test

    The design of experiments is shown in Table 1. In the experiment, different levels of fructose (Crystalline fructose 99.5%, Kato Kaguku Co., Japan) or sucrose (Daesang Co, Korea) were administered to normal SD and type 2 diabetic GK rats as supplements to test their effects on blood glucose regulation using the OGGT.

    Table 1
    Experimental design of the Study

    After the rats had fasted for 12 h, a 50% glucose solution (1 g/kg of body weight) with the supplement of fructose or sucrose at different levels (0.05 g/kg, 0.1 g/kg or 0.4 g/kg body weight) was orally administered, and blood was taken from the tail vein at 0 (before the solution load), 30, 60, 90 and 120 min afterward (The Korean Society of Food Science and Nutrition, 2000). Blood glucose concentrations were determined immediately using an Accu-chek (Roche Diagnostics, Germany). According to studies on the OGTT in which glucose solution is added with fructose, the typical amount of fructose added is about 10% (w/w) of the glucose solution. Moreover, adding a smaller proportion of fructose was shown to be more effective in observing the regulating effect on blood glucose than adding a larger amount (Moore et al., 2000). For these reasons, we set the fructose amount to be added to the glucose solution to 5% and 10% (w/w) of the glucose solution in this study. These amounts correspond to 0.05 g and 0.1 g per kg of body weight, respectively, for the glucose solution at 1 g per kg of body weight. For completeness, we also tested the case in which the added fructose amount was greater than 10% (w/w) of the glucose solution. In this case, fructose was 0.4 g per kg of body weight derived from the intake of added sugar, which is the equivalent of 19.1 g per day for a normal 60 kg adult Korean (Dietary Reference Intakes for Koreans, 2005). The increment in blood glucose after the glucose load was expressed in terms of AUC from the time when the fasting blood was drawn until 120 min postload blood sampling. AUC was calculated by WinNolin program (version 1.1, Pharsight Co., USA).

    Statistical Analysis

    All statistical analyses were performed by the SAS program package version 9.1. All results were expressed as the mean ± standard error (SE). The data were analyzed by one-way analysis of variance (ANOVA) and differences between experimental groups were evaluated using Duncan's multiple range tests at the p<0.05 significance level.

    Results

    Oral glucose tolerance in normal rats

    Daily food intake and body weight change per week in SD rats were not significantly different among any groups. In this study, the range of daily food intake and body weight change per week were 29.85~33.36 g/day and 3.79~4.55 g/day, respectively. The OGTT results for SD rats are shown in Fig. 1. There was no significant difference in the glucose response between the acute fructose and sucrose administered groups. At 30 min and 60 min after solution ingestion, although there were no significant differences between treatments, blood glucose concentrations of rats administered the 0.1F or 0.4F diets tended to be lower than those of the rats administered the 0.1S or 0.4S levels, respectively. At 90 min and 120 min after solution ingestion, the blood glucose concentrations of the fructose-administered groups tended to be lower than those of the sucrose-administered groups at matching concentration. Supplement of fructose to the glucose load tended to reduce the glycemic response to the OGTT.

    Fig. 1
    The changes in blood glucose concentration during an oral glucose tolerance test in SD rats

    The AUC data of the glucose response in SD rats is shown in Fig. 2. There was no significant difference in the AUC of the glucose response between acute fructose- and sucrose-administered groups, whereas the AUCs of fructose-administered groups tended to be smaller than those of control or sucrose-administered groups at matching concentration. The AUCs of lower-level fructose- or sucrose-administered groups tended to be smaller than those of groups administered higher levels of fructose or sucrose at matching concentration. The AUCs of the 0.05F, 0.1F, 0.4F and 0.05S groups tended to be smaller than that of the control group, and the AUC of the 0.05F group was the smallest. The AUCs of fructose-administered groups tended to be smaller than those of the sucrose-administered groups. The AUC of the glucose response, calculated as the change from basal values in each group, was about 0.01% smaller with the 0.05F diet than with the 0.05S diet. It was 7% smaller with the 0.1F diet than with the 0.1S diet and 10% smaller with the 0.4F diet than with the 0.4S diet. The AUC of the glucose response was about 10% smaller with the 0.05F diet than with the control diet. The supplement of fructose to the glucose load tended to improve glucose tolerance in these SD rats.

    Fig. 2
    The areas under the curve of the glucose response in SD rats

    Oral glucose tolerance in diabetic rats

    Daily food intake and body weight change per week in GK rats were not significantly different among any groups. In this study, the range of daily food intake and body weight change per week was 14.67~15.59 g/day and 4.59~5.19 g/day, respectively. The OGTT data for GK rats are shown in Fig. 3. There was no significant difference in the glucose response between the acute fructose- and sucrose-administered groups. At 30 min after solution ingestion, blood glucose concentrations of the sucrose-administered groups were higher than those of the fructose-administered groups. At 60, 90 and 120 min after solution ingestion, blood glucose concentrations of the fructose-administered groups tended to be lower than those of sucrose-administered groups at matching concentration, except for the 0.1F and 0.1S groups at 60 min. At 30 and 60 min, the blood glucose concentrations of the control group tended to be lower than those of the experimental groups. At 90 and 120 min, the blood glucose concentration of the 0.05F group tended to be lower than those of the other groups. Supplement of fructose to the glucose load, compared with supplement of sucrose to the glucose load, tended to reduce the glycemic response to the OGTT. In contrast to data for normal animals, diabetic rats should be higher blood glucose level during the first 120 min after 12 hr of fasting than normal rats. Furthermore, while the blood glucose level of normal rats was peaked at around after 30 min from 12 hr of fasting, that of diabetic rats was peaked after 30 min to 60 min from 12 hr of fasting.

    Fig. 3
    The changes of blood glucose concentration during oral glucose tolerance test in GK rats

    The AUCs of the glucose response in GK rats are shown in Fig. 4. There were no significant differences between the acute fructose- and sucrose-administered groups, whereas the AUCs of fructose-administered groups tended to be smaller than those of the control or sucrose-administered groups at matching concentration. The AUCs of higher-level fructose- or sucrose-administered groups tended to be larger than those of rats administered lower-level fructose or sucrose diets, except for the 0.05S and 0.1S groups. Only the AUC of the 0.05F administered group tended to be smaller than that of the control group. The AUC was the smallest in the 0.05F group, followed by the control, 0.1F, 0.4F and sucrose-administered groups. The AUC of glucose response, calculated as the change from basal values in each group, was approximately 7% smaller with the 0.05F diet than with the 0.05S diet, 6% smaller with the 0.1F diet than with the 0.1S diet, and 6% smaller with the 0.4F diet than with the 0.4S diet. The AUC of the glucose response was about 0.7% smaller with the 0.05F diet than with the control diet. Consequently, the AUCs of fructose-administered groups tended to be smaller than those in the sucrose-administered groups, and the AUCs of the lowest-level fructose-administered groups were the smallest. In conclusion, the supplement of a small amount of fructose to a glucose load, compared with supplement of a small amount of sucrose to a glucose load, tended to improve glucose tolerance in GK rats with type 2 diabetes.

    Fig. 4
    The areas under the curve of the glucose response in GK rats

    Discussion

    In this study, different levels of fructose or sucrose were administered to normal SD and type 2 diabetic GK rats as supplements to test their effects on blood glucose regulation, using the OGTT. The present study implies that the addition of fructose seems more attributive to blood glucose regulation regardless of the added amount in comparison with sucrose administration. Moreover, in our present study where we conducted adding three different amounts of fructose, the results imply that smaller amount of added fructose induces more effective blood glucose regulation while not significantly. Had fructose been added more consistently over a period of time, as opposed to just once as done in this study, a clearer effect of fructose administration in blood glucose regulation might have been observed in agreement with the known results in the literature. Furthermore, we also expect to observe a more definitive result had we used mid-aged rats that have difficulty in blood glucose regulation as opposed to young rats as done in this study. In the future, more extensive experiments regarding the blood glucose regulation need be explored. The fact that supplemental fructose contributing to blood glucose regulation can be explained from metabolic adaptation-in other words, the ability to suppress endogenous glucose production during hyperglycemia and increased net hepatic glucose uptake and metabolism in normal subjects. There are various studies on the effect of supplement of fructose or sucrose to blood glucose in OGTTs in which fructose or sucrose was added to the glucose load in normal subjects. Moore et al. (2000) examined the effect of fructose on glucose tolerance in 11 normal human volunteers. Each volunteer underwent an OGTT that consisted of 75 g of glucose with or without 7.5 g of fructose on two separate experiments at least one week apart. The OGTT with fructose in comparison with that without fructose showed significantly smaller AUC of the change in plasma glucose (p<0.05). Low-dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride responses. The increase in the arterial blood glucose concentration during fructose infusion was only half as great as it was in the absence of fructose (Shiota et al., 2002). In that study, the increased glycolytic flux associated with the inclusion of fructose was probably secondary to an increase in the intracellular glucose 6-phosphate content. This in general is secondary to the activation of glucokinase, perhaps with an associated increase in the activity of phosphofructokinase (Shiota et al., 2002). A small proportion of ingested fructose generally improves glycemic control because it increases net hepatic glucose uptake via enhanced translocation of glucokinase, increased hepatic glycogen synthesis and hepatic glycolysis (Petersen et al., 2001). Increased amount of added fructose resulted in a reduced blood glucose regulating effect. The fact that an increased supplement of fructose translates to extra calories, which transform to glucose and eventually to a higher blood glucose level, can account for this (Faeh et al., 2005). If fructose intake is very high, or if it leads to excessive energy consumption, it can have an adverse effect on glucose regulation (Levi & Werman, 1998).

    There have been studies on the effects of supplement with fructose or sucrose on the blood glucose level during OGTTs in diabetic subjects. In the present study, we observed that the AUC of only the 0.05F group tended to be smaller than that of the control group. The blood glucose regulations of sucrose-administered groups tended to be poorer than those of the fructose-administered groups. Unlike the normal animals, higher fructose supplement in the diabetic rats had adverse effects on blood glucose regulation compared with control group. For diabetic animals, insulin secretion becomes uncontrollable after an intake of high amount of sugar, and the ability to suppress endogenous glucose production during hyperglycemia becomes impaired. These experimental results suggest that higher doses of fructose increase the blood glucose level and that only small doses of fructose will have beneficial effects on blood glucose regulation in diabetic subjects. Moore et al. (2001) studied five adults with type 2 diabetes who underwent an OGTT that consisted of 75 g of glucose with or without 7.5 g of fructose on two separate experiments that took place at least one week apart. The subjects with type 2 diabetes demonstrated a 14% reduction in the AUC of the glucose response to an OGTT when a small dose of fructose was added to the glucose load. The improvement in glucose tolerance with fructose ingestion in this study did not occur at the expense of increased insulin secretion. Wolf et al. (2002) evaluated the effects of supplemental fructose on postprandial glycemia in an animal model. After overnight food deprivation, Zucker fatty (fa/fa) rats were given a meal glucose tolerance test. At a dose of 0.16 g/kg body weight, fructose reduced the AUC by 34% when supplemented to a glucose challenge (1 g/kg). In a dose-response study (0.1, 0.2 and 0.5 g/kg body weight), supplemental fructose reduced the peak rise in plasma glucose (p<0.01). A low dose of fructose (0.075 g/kg body) reduced (p<0.05) the AUC by 18%. These findings have great clinical potential for the prevention of postprandial hyperglycemia in people with diabetes. Atkinson et al (2000) reported that supplemental fructose (1, 2 and 4 g/kg body weight) reduced (p<0.05) the early (10 min) postprandial plasma glucose concentrations after a glucose challenge. However, the incremental AUC for plasma glucose was unaffected.

    The mechanism by which a small dose of fructose can decrease the blood glucose level in normal rats may be explained as follows. When glucose and fructose are supplemented together, they compete for GLUT2 which exists in the apical surface so that fructose is induced to suppress the absorption of glucose. Recently, Kellett and Brot-Laroche (2005) have discovered a new pathway of sugar absorption, the apical GLUT2 pathway. GLUT2 is an attractive candidate as the dominant sugar transporter because it is a high-capacity transporter, has a much higher Km for glucose and fructose, and transports both substrates (Kellet & Brot-Laroche, 2005; Kwon et al., 2007). In the classical model, GLUT2 has an exclusively basolateral location. But, more recent localization data showed that GLUT2 localizes to the apical surface. Binding sites on GLUT2 for fructose and glucose are the same (Corpe et al., 1996; Kellett & Helliwell, 2000). Higher blood glucose level and less effective blood glucose regulation were observed when we performed OGTT to diabetic rats than to normal rats. This can be accounted for by the impaired insulin secretion which leads to reduced translocation of GLUT4 in diabetic rats. The latter is associated with decreased glucose transport in type 2 diabetic rats (Watson & Pessin, 2001; Wood & Trayhum, 2003). Increased supplement with fructose translates to extra calories, which in turn transforms to glucose. Eventually, these higher blood glucose levels can account for this reduced regulation.

    We concluded from this experiment that fructose has tendency to be more effective in blood glucose regulation than sucrose, and moreover, that smaller amount of fructose is preferred to larger amount. Specifically, our experiments indicated that the fructose level of 0.05 g/kg body weight as dietary supplement was the most effective amount for blood glucose regulation from the pool of 0.05 g/kg, 0.1 g/kg and 0.4 g/kg body weights. Therefore, our results suggest the use of fructose as the substitute sweetener for sucrose, which may be beneficial for blood glucose regulation.

    Notes

    This research was supported by grants from Daesang.Co.Ltd and the second stage of Brain Korea 21 project in 2006.

    References

      1. Atkinson AM, Leighton B, Brocklehurst KJ, Wightman HM, Vertigan HL, Hargreaves RB, Warner P, Waddell ID. Acute administration of fructose, with glucose, causes a significant decrease in early plasma glucose levels in rodents. Diabetes 2000;49:A278.
      1. Bantle JP, Laine DC, Castle GW, Thomas JW, Hoogwerf BJ, Goetz FC. Postprandial glucose and insulin responses to meals containing different carbohydrates in normal and diabetic subjects. N Engl J Med 1983;309:7–12.
      1. Bantle JP, Laine DC, Thomas JW. Metabolic effects of dietary fructose and sucrose in type I and II diabetic subjects. JAMA 1986;256:3241–3246.
      1. Bantle JP. Clinical aspects of sucrose and fructose metabolism. Diabetes Care 1989;12:56–61.
      1. Basciano H, Federico L, Adeli K. Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2005;2:5.
      1. Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004;79:537–543.
      1. Cannon MC, Nuttall FQ, Krezowski PA, Billington CJ, Parker S. The serum insulin and plasma glucose responses to milk and fruit products in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1986;29:784–791.
      1. Centers for Disease Control and Prevention NCfHS, Division of Health Interview Statistics. Census of the population and population estimates. Hyattsville, MD: Centers for Disease Control and Prevention; 1997.
      1. Ciok J, Dolna A. The role of glycemic index concept in carbohydrate metabolism. Przegl Lek 2006;63:287–291.
      1. Corpe CP, Basaleh MM, Affleck J, Gould G, Jess TJ, Kellett GL. The regulation of GLUT5 and GLUT2 activity in the adaptation of intestinal brush-border fructose transport in diabetes. Pfluegers Arch 1996;432:192–201.
      1. Crapo PA, Kolterman OG. The metabolic effects of 2-week fructose feeding in normal subjects. Am J Clin Nutr 1984;39:525–534.
      1. Curry DL. Effect of mannose and fructose on the synthesis and secretion of insulin. Pancreas 1989;4:2–4.
      1. Ministry of Health and Welfare. The Korean Nutrition Society. Dietary reference intakes for Koreans. Seoul. Republic of Korea: The Korean Nutrition Society; 2005. pp. 0-409.
      1. Faeh D, Minehira K, Schwarz JM, Periasamy R, Park S, Tappy L. Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in normal men. Diabetes 2005;54:1907–1913.
      1. Hasegawa K, Larson JL, White WJ, Clifford CB. In: Baseline data comparing CD(SD)IGS rats supplied from Charles River Japan, Charles River UK and Charles River USA. Yokohama. Japan: CD(SD)IGS study group; 2001. pp. 9-18.
      1. Henry RR, Crapo PA, Thorburn AW. Current issues in fructose metabolism. Annu Rev Nutr 1991;11:21–39.
      1. Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension 1987;10:512–516.
      1. Jeckins DJA, Wolever TMS, Taylor RH, Barker H, Fielden H, Baldwin JM, Bowling AC, Newman HC, Jenkins AL, Goff DV. Glycemic index of foods, a physiological basis for carbohydrate exchange. Am J Clin Nutr 1981;34:362–366.
      1. Jurgens H, Haass W, Castaneda TR, Schurmann A, Koebnick C, Dombrowski F, Otto B, Nawrocki AR, Scherer PE, Spranger J, Ristow M, Joost HG, Havel PJ, Tschop MH. Consuming fructose-sweetened beverages increases body adiposity in mice. Obes Res 2005;13:1146–1156.
      1. Kasim-Karakas SE, Vriend H, Almario R, Chow LC, Goodman MN. Effects of dietary carbohydrates on glucose and lipid metabolism in golden Syrian hamsters. J Lab Clin Med 1996;128:208–213.
      1. Kellett GL, Brot-Laroche E. Apical GLUT2: a major pathway of intestinal sugar absorption. Diabetes 2005;54:3056–3062.
      1. Kellett GL, Helliwell PA. The diffusive component of intestinal glucose absorption is mediated by the glucose induced recruitment of GLUT2 to the brush-border membrane. Biochem J 2000;350:155–162.
      1. Koivisto VA. Fructose as a dietary sweetener in diabetes mellitus. Diabetes Care 1978;1:241–246.
      1. Food balance sheet. Korea Rural Economic Institute. 2004 [Accessed on 2004].
        http://www.kosis.kr.
      1. Koyama M, Wada R, Sakuraba H, Mizukami H, Yagihashi S. Accelerated loss of islet β cells in sucrose-fed Goto-Kakizaki rats, a genetic model of non-insulin-dependent diabetes mellitus. Am J Pathol 1998;153:537–545.
      1. Kwon O, Eck P, Chen S, Corpe CP, Lee JH, Kruhlak M, Levine M. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. FASEB J 2007;21:366–377.
      1. Levi B, Werman MJ. Long-term fructose consumption accelerates glycation and several age-related variables in male rat. J Nutr 1998;128:1442–1449.
      1. Ludwig DS, Pereira MA, Kroenke CH, Hilner JE, VanHorn L, Slattery ML, Jacobs DR. Dietary fiber, weight gain, and cardiovascular risk factors in young adults. J Am Med Assoc 1999;282:1539–1546.
      1. Mayer PA. Intermediary metabolism of fructose. Am J Clin Nutr 1993;58:754S–765S.
      1. Report on 1998 National Health and Nutrition Survey: Nutrition Survey. Ministry of Health and Welfare. 1999 [Accessed on 1999].
        http://library.mohow.go.kr.
      1. Report on 2005 National Health and Nutrition Survey: Nutrition Survey. Ministry of Health and Welfare. 2006 [Accessed on 10/20/2006].
        http://www.mw.go.kr/user.tdf.
      1. Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP. The continuing epidemics of obesity and diabetes in the United States. JAMA 2001;286:1195–1200.
      1. Mokdad AH, Ford ES, Bowman BA, Nelson DE, Engelgau MM, Vinicor F, Marks JS. Diabetes trends in the US: 1990-1998. Diabetes Care 2000;23:1278–1283.
      1. Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States, 1991-1998. JAMA 1999;282:1519–1522.
      1. Moore MC, Cherrington AD, Mann SL, Davis SN. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults. J Clin Endocrinol Metab 2000;85:4515–4519.
      1. Moore MC, Davis SN, Mann SL, Cherrington AD. Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes. Diabetes Care 2001;24:1882–1887.
      1. Nutrition Subcommittee of the British Diabetic Association's Professional Advisory Committee. Sucrose and fructose in the diabetic diet. Diabet Med 1990;7:764–769.
      1. Olefsky JM, Crapo P. Fructose, xylitol and sorbitol. Diabetes Care 1980;3:390–393.
      1. Ostenson C-G, Abdel-Halim SM, Andersson A, Efendic S. Studies on the pathogenesis of NIDDM in the GK (Goto-Kakizaki) rat. In: Shafrir E, editor. Lessons from Animal Diabetes. VI. Boston. USA: Birkhäuser; 1996. pp. 299-315.
      1. Ostenson C-G, Khan A, Abdel-Halim SM, Guenifi A, Suzuki K, Goto Y, Efendic S. Abnormal insulin secretion and glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat. Diabetologia 1993;36:3–8.
      1. Pankowska E, Szypowska A, Lipka M. The evolution of insulin therapy and new insight into nutrition recommendations for individuals with diabetes. Przegl Lek 2006;63:284–286.
      1. Pan XR, Yang WY, Li GW, Liu J. Prevalence of diabetes and its risk factors in China, 1994. National Diabetes Prevention and Control Cooperative Group. Diabetes Care 1997;20:1664–1669.
      1. Petersen KF, Laurent D, Yu C, Cline GW, Shulman GI. Stimulating effects of low-dose fructose on insulin-stimulated hepatic glycogen synthesis in humans. Diabetes 2001;50:1263–1268.
      1. Portha B, Serradas P, Bailbe D, Suzuki K, Goto Y, Giroix M-H. β-cell sensitivity to glucose in the GK rat, a spontaneous nonobese model for type II diabetes. Diabetes 1991;40:486–491.
      1. Ramachandran A, Snehalatha C, Latha E, Vijay V, Viswanathan M. Rising prevalence of NIDDM in an urban population in India. Diabetologia 1997;40:232–237.
      1. Salmeron J, Ascherio M, Rimm EB, Colditz GA, Spiegelman D, Jenkens DJ, Stampfer MJ, Wing AL, Willett WC. Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care 1997a;20:545–550.
      1. Salmeron J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA 1997b;277:472–477.
      1. Salmeron J, Jenkins DJ, Ascherio A. Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care 1997c;20:545–550.
      1. Sato Y, Ito T, Udaka N, Kanisawa M, Noguchi Y, Cushman SW, Satoh S. Immunohistochemical localization of facilitated-diffusion glucose transporters in rat pancreatic islets. Tissue Cell 1996;28:637–643.
      1. Schauberger G, Brinck UC, Guldner G, Spaethe R, Niklas L, Otto H. Exchange of carbohydrates according to their effect on blood glucose. Diabetes 1977;26:415.
      1. Shiota M, Moore MC, Galassetti P, Monohan M, Neal DW, Shulman GI, Cherrington AD. Inclusion of low amounts of fructose with an intraduodenal glucose load markedly reduces postprandial hyperglycemia and hyperinsulinemia in the conscious dog. Diabetes 2002;51:469–478.
      1. Swan DC, Davidson P, Albrink MJ. Effect of simple and complex carbohydrates on plasma non-esterified fatty acids, plasma sugar, and plasma insulin during oral carbohydrate tolerance tests. Lancet 1966;1:60–63.
      1. The Korean Nutrition Society. The actual condition and management of obesity of people in Korea. Fall Conference of the Korean Nutrition Society; Seoul. Republic of Korea: The Korean Nutrition Society; 2006.
      1. The Korean Society of Food Science and Nutrition. Handbook of experiments in food science and nutrition: Nutrition. Seoul. Republic of Korea: Hyoil Press Co.; 2000.
      1. Truswell AS. Glycaemic index of foods. Eur J Clin Nutr 1992;46:S91–S101.
      1. Uusitupa MI. Fructose in the diabetic diet. Am J Clin Nutr 1994;59:753S–757S.
      1. Watson RT, Pessin JE. Subcellular compartmentalization and trafficking of the insulin-responsive glucose transporter, GLUT4. Exp Cell Res 2001;271:75–83.
      1. Wolf BW, Humphrey PM, Hadley CW, Maharry KS, Garleb KA, Firkins JL. Supplemental fructose attenuates postprandial glycemia in Zucker fatty fa/fa rats. J Nutr 2002;132:1219–1223.
      1. Wood IS, Trayhum P. Glucose transporters (GLUT and SGLUT): expanded families of sugar transport proteins. Br J Nutr 2003;89:3–9.
      1. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001;414:782–787.
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    MeSH Terms
    Animals
    Area Under Curve
    Blood Glucose
    Body Weight
    Dietary Supplements
    Fructose
    Glucose
    Glucose Tolerance Test
    Rats
    Sucrose
    Sweetening Agents
    Metrics
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