The membrane vertical phase separation hypothesis predicts that a decrease in plasma membrane acyl chain order will increase major histocompatibility complex (MHC) class I surface expression. The hypothesis is based on modification of plasma membrane acyl chain order in cell culture and has not been tested in vivo. In the present study, we isolated splenic B cells from C57/BL6 mice fed either a normal diet or high-fat diets enriched in SFA or MUFA and assayed for changes in plasma membrane acyl chain order and MHC class I surface expression. Plasma membranes of B cells from MUFA-fed mice had significantly decreased acyl chain order and increased headgroup order. The decrease in acyl chain order correlated with a significant increase in the acyl chain unsaturation of B cells from the MUFA-fed mice. MHC class I surface levels on B cells were not affected by the MUFA-rich diet. This study suggests that the membrane vertical phase separation hypothesis may have limited application in a physiologically relevant setting.

Ethnicity-related differences in maternal n-3 and n-6 fatty acid status may be relevant to ethnic disparities in birth outcomes observed worldwide. The present study explored differences in early pregnancy n-3 and n-6 fatty acid composition of maternal plasma phospholipids between Dutch and ethnic minority pregnant women in Amsterdam, the Netherlands, with a focus on the major functional fatty acids EPA (20 : 5n-3), DHA (22 : 6n-3), dihomo-γ-linolenic acid (DGLA; 20 : 3n-6) and arachidonic acid (AA; 20 : 4n-6). Data were derived from the Amsterdam Born Children and their Development (ABCD) cohort (inclusion January 2003 to March 2004). Compared with Dutch women (n 2443), Surinamese (n 286), Antillean (n 63), Turkish (n 167) and Moroccan (n 241) women had generally lower proportions of n-3 fatty acids (expressed as percentage of total fatty acids) but higher proportions of n-6 fatty acids (general linear model; P < 0·001). Ghanaian women (n 54) had higher proportions of EPA and DHA, but generally lower proportions of n-6 fatty acids (P < 0·001). Differences were most pronounced in Turkish and Ghanaian women, who, by means of a simple questionnaire, reported the lowest and highest fish consumption respectively. Adjustment for fish intake, however, hardly attenuated the differences in relative EPA, DHA, DGLA and AA concentrations between the various ethnic groups. Given the limitations of this observational study, further research into the ethnicity-related differences in maternal n-3 and n-6 fatty acid patterns is warranted, particularly to elucidate the explanatory role of fatty acid intake v. metabolic differences.

The present study aimed to investigate the effects of two lactation sow feeds, differing in n-6:n-3 ratio, given to sows before parturition on body condition and feed intake, periparturient metabolism (leptin, insulin, triiodothyronine (T3) and thyroxine (T4)), inflammatory parameters (TNFα, IL-6, serum amyloid A (SAA)) and on piglet performance (birth weight, survivability). The feed contained either a low (supplemented with fish oil; f groups) or high (supplemented with sunflower-seed oil; s groups) n-6:n-3 ratio and was administered from 8 d (f8, s8) or 3 d (f3, s3) before parturition until weaning. The level of inclusion of the oil sources was 2 %. Seventy-two sows were randomly allocated 8 d before expected farrowing into four groups: f3, f8, s3, s8. Type of feed had a significant influence on the sows' feed intake during the first 2 d of lactation (s < f), leptin on days 4, 3 and 2 before parturition (f < s), insulin on day 1 after parturition (f < s), T4 on the day before parturition (s < f) and rectal temperature on the day after parturition (f < s). Onset of administration of the feed (3 v. 8 d) had significant effects on leptin on day 2 before parturition (8 < 3), insulin on day 4 before parturition (3 < 8), T3 on day 4 before parturition and on the day after parturition (3 < 8), SAA on day 3 after parturition (8 < 3) and piglet weight during the first days postpartum (3 < 8). In conclusion, under the present conditions, a lactation feed low in n-6:n-3 ratio administered from 8 d before farrowing ensures improved feed intake during the first days postpartum and was associated with a better metabolic change and inflammatory profile in sows in the periparturient period.

The periparturient relaxation of immunity (PPRI) against parasites in ewes has a nutritional basis. We investigated whether ewes experience a reduction in food intake (anorexia) during PPRI and if the magnitude of anorexia is affected by host production potential and dietary protein supplementation. We also investigated whether nematode infection is linked to plasma leptin concentrations in periparturient ewes. The experiment was a 2 × 2 × 2 factorial design. Two breeds of twin-bearing/lactating ewes (Greyface cross, G (n 32) and Scottish Blackface, B (n 32)) were used. Half of the ewes were trickle infected with 30 000 larvae of the abomasal parasite Teladorsagia circumcincta per week and the other half were not. During the experiment, all ewes had ad libitum access to a low-protein diet that provided less protein than the recommended allowance. In addition, half of the ewes received a protein supplement that resulted in protein intakes that exceeded recommendations. Nematode infection resulted in a breakdown of immunity to parasites and a reduction in food intake in both breeds. The breeds differed in the extent of PPRI (G ewes having higher faecal egg counts than B ewes), but not in the magnitude of anorexia. Protein supplementation resulted in a reduction in faecal egg counts, but had no effect on the magnitude of anorexia. Plasma leptin concentrations changed significantly over time, but were not affected by protein supplementation or infection. It is concluded that infection with T. circumcincta in periparturient ewes results in anorexia that is not alleviated by protein supplementation and seems unrelated to plasma leptin concentrations.

Diabetes mellitus is an important risk factor for CVD. A previous study showed that high glucose induced the apoptosis of human umbilical vein endothelial cells (HUVEC) via the sequential activation of reactive oxygen species, Jun N-terminal kinase (JNK) and caspase-3. The apoptosis cascade could be blocked by ascorbic acid at the micromolar concentration (100 μm). In addition to ascorbic acid, quercetin, the most abundant dietary flavonol, has been recently actively studied in vascular protection effects due to its antioxidant effect at low micromolar concentrations (10–50 μm). Quercetin sulfate/glucuronide, the metabolite of quercetin in blood, however, has been rarely evaluated. In the present study, we investigated the effect of quercetin sulfate/glucuronide on the prevention of high glucose-induced apoptosis of HUVEC. HUVEC were treated with media containing high glucose (33 mm) in the presence or absence of ascorbic acid (100 μm) or quercetin sulfate/glucuronide (100 nm, 300 nm and 1 μm). For the detection of apoptosis, a cell death detection ELISA assay was used. The level of intracellular H2O2 was measured by flow cytometry. JNK and caspase-3 were evaluated by a kinase activity assay and Western blot analysis. The results showed that high glucose-induced apoptosis was inhibited by quercetin sulfate/glucuronide in a dose-dependent manner. The effect of quercetin sulfate/glucuronide on H2O2 quenching, inhibition of JNK and caspase-3 activity at the nanomolar concentration (300 nm) was similar to that of ascorbic acid at the micromolar concentration (100 μm). The findings of the present study may shed light on the pharmacological application of quercetin in CVD.

The aim of this study was to describe the effects of two diets differing in n-6:n-3 ratio and prepartal feeding regime on gene expression of PPARγ1a/1b, PPARγ1c/1d, PPARγ2, PPARγ coactivator 1A (PPARGC1A), GLUT4, TNFα, adiponectin, leptin, leptin receptor (LEPR), fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL) in sows' white adipose tissue on the first day of lactation. The relationship between mRNA expression of these genes and circulating insulin, leptin and thyroid hormones was also considered. Diets contained a low (supplemented with fish oil; f group) or a high (supplemented with sunflower oil; s group) n-6:n-3 ratio and were provided from 8 (f8, s8) or 3 d (f3, s3) before parturition (onset day 8 or 3). A low n-6:n-3 ratio reduced the 1 d postpartum expression of PPARγ2 and PPARGC1A but only when applied from 3 d before parturition. Circulating leptin was negatively correlated with mRNA expression of adiponectin, LEPR and LPL, whereas thyroxine was positively correlated with levels of PPARGC1A. In conclusion, the effect of dietary treatments, e.g. altering the n-6:n-3 ratio, around parturition on the expression of crucial genes in nutrient metabolism can be modulated by the duration of application before parturition.

Plasma concentrations of vitamin E and carotenoids are governed by several factors, including genetic factors. Single nucleotide polymorphisms (SNP) in some genes involved in lipid metabolism have recently been associated with fasting plasma concentrations of these fat-soluble micronutrients. To further investigate the role of genetic factors that modulate the plasma concentrations of these micronutrients, we assessed whether SNP in five candidate genes (apo C-III, CETP, hepatic lipase, I-FABP and MTP) were associated with the plasma concentrations of these micronutrients. Fasting plasma vitamin E and carotenoid concentrations were measured in 129 French Caucasian subjects (forty-eight males and eighty-one females). Candidate SNP were genotyped by PCR amplification followed by restriction fragment length polymorphisms. Plasma γ-tocopherol, α-carotene and β-carotene concentrations were significantly different (P < 0·05) in subjects who carried different SNP variants in hepatic lipase. Plasma α-tocopherol concentrations were significantly different in subjects who had different SNP variants in apo C-III and cholesteryl ester transfer protein (CETP). Plasma lycopene concentrations were significantly different (P < 0·05) in women who had different SNP variants in intestinal fatty acid binding protein (I-FABP). Finally, there was no effect of SNP variants in microsomal TAG transfer protein upon the plasma concentrations of these micronutrients. Most of the observed differences remained significant after the plasma micronutrients were adjusted for plasma TAG and cholesterol. These results suggest that apo C-III, CETP and hepatic lipase play a role in determining the plasma concentrations of tocopherols while hepatic lipase and I-FABP may modulate plasma concentrations of carotenoids.

The present study investigates the benefits of the dietary intake of chia seed (Salvia hispanica L.) rich in α-linolenic acid and fibre upon dyslipidaemia and insulin resistance (IR), induced by intake of a sucrose-rich (62·5 %) diet (SRD). To achieve these goals two sets of experiments were designed: (i) to study the prevention of onset of dyslipidaemia and IR in Wistar rats fed during 3 weeks with a SRD in which chia seed was the dietary source of fat; (ii) to analyse the effectiveness of chia seed in improving or reversing the metabolic abnormalities described above. Rats were fed a SRD during 3 months; by the end of this period, stable dyslipidaemia and IR were present in the animals. From months 3–5, half the animals continued with the SRD and the other half were fed a SRD in which the source of fat was substituted by chia seed (SRD+chia). The control group received a diet in which sucrose was replaced by maize starch. The results showed that: (i) dietary chia seed prevented the onset of dyslipidaemia and IR in the rats fed the SRD for 3 weeks – glycaemia did not change; (ii) dyslipidaemia and IR in the long-term SRD-fed rats were normalised without changes in insulinaemia when chia seed provided the dietary fat during the last 2 months of the feeding period. Dietary chia seed reduced the visceral adiposity present in the SRD rats. The present study provides new data regarding the beneficial effect of chia seed upon lipid and glucose homeostasis in an experimental model of dislipidaemia and IR.

Negative consumer opinion poses a potential barrier to the application of nutrigenomic intervention. The present study has aimed to determine attitudes toward genetic testing and personalised nutrition among the European public. An omnibus opinion survey of a representative sample aged 14–55+ years (n 5967) took place in France, Italy, Great Britain, Portugal, Poland and Germany during June 2005 as part of the Lipgene project. A majority of respondents (66 %) reported that they would be willing to undergo genetic testing and 27 % to follow a personalised diet. Individuals who indicated a willingness to have a genetic test for the personalising of their diets were more likely to report a history of high blood cholesterol levels, central obesity and/or high levels of stress than those who would have a test only for general interest. Those who indicated that they would not have a genetic test were more likely to be male and less likely to report having central obesity. Individuals with a history of high blood cholesterol were less likely than those who did not to worry if intervention foods contained GM ingredients. Individuals who were aware that they had health problems associated with the metabolic syndrome appeared particularly favourable toward nutrigenomic intervention. These findings are encouraging for the future application of personalised nutrition provided that policies are put in place to address public concern about how genetic information is used and held.

Vitamin E is divided into two subgroups; tocopherols and tocotrienols. Both have protective roles in biological systems. The present study was conducted to compare the effect of short-term supplementation at 200 mg/d of either α-tocopherol or a tocotrienol-rich fraction (TRF) from palm oil on immune modulation and plasma vitamin E levels in normal healthy Asian volunteers. In a randomised, double-blind placebo-controlled trial conducted, fifty-three healthy volunteers aged 20–50 years were recruited based on the study's inclusion and exclusion criteria. They were randomly assigned into three groups, i.e. two experimental groups that received daily supplementation at 200 mg of either α-tocopherol or the TRF, and the control group that received a placebo. Blood was drawn on days 0, 28 and 56 for several laboratory analyses. Differences in the production of IL-4 or interferon-γ by concanavalin A-stimulated lymphocytes isolated from these volunteers were not significant (P>0·05). There were no significant differences observed in immune parameters between the healthy volunteers who received daily supplementation with either α-tocopherol or the TRF. As these observations were made in the absence of any immunogenic challenge, we feel it would be of benefit to study if there would be any differences observed when an immunogenic challenge such as vaccination were introduced.

The aim of this work was to assess the effects of a high-fat diet enriched in Ca, which accompanies lower body fat deposition, on mineral depots, as well as to assess the potential role of adaptive thermogenesis in mice. Male mice were fed ad libitum a high-fat (43 %) diet with a Ca content of 4 g/kg from calcium carbonate (control group) or 12 g/kg (42 % from milk powder and the rest from calcium carbonate) (Ca group) for 56 d. Body weight, food intake and urine were periodically collected. Tissue samples were collected when the mice were killed and the composition was determined. Expression of uncoupling proteins was determined by Western blotting. Mineral content was measured by flame atomic absorption spectrometry. Lower body weight gain and fat accretion was found in the Ca group. This could not be attributable to lower gross energy intake or to activation of adaptive thermogenesis. Although significant urine mineral loss was found in the Ca group, preservation of mineral depots in bone was observed. Our data support the fact that adding more Ca to the diet, using a combination of calcium carbonate plus milk powder containing among other things higher Zn and Mg, contributes to counteracting obesity and improving lipid metabolism.

The present research was conducted within the framework of the EURopean micronutrient RECommendations Aligned project. In order to identify the best practice in assessing nutrient intakes, a search strategy for collecting data from national food consumption surveys/studies in Europe was developed. Systematic literature searches were carried out on twenty-eight European and the four European Free Trade Association countries. A questionnaire was also sent to two to five experts in each country. Systematic reviews using PubMed yielded 12 703 abstracts that were reduced to 200 studies using inclusion and exclusion criteria. Similarly, a search of ministry web sites yielded 3033 hits, and subsequently reduced to nine surveys. Belgium, France, Germany, Ireland, Sweden, Spain and the United Kingdom were the countries with most data and Slovenia and Liechtenstein were those with the least. Seventy-eight expert questionnaires were obtained from all countries except for Liechtenstein, Luxembourg and Slovakia. Detailed results and references are given. A systematic search and questionnaires are equally good at identifying national surveys across countries. Literature searching provides globally accessible and objective information albeit limited, whereas the questionnaire provides information that, depending upon responders, can be more complete. A combination of both strategies is recommended.

Mice fed with diet containing 0·5 % cholesterol for 10 weeks resulted in cholesterol supersaturation in gallbladder bile which promoted the formation of cholesterol gallstones (CGS). In this study, dietary hypocholesterolaemic spices, garlic and onion (both raw or heat-processed) were examined for their antilithogenic potential by including at 0·6 and 2·0 % level, respectively, along with lithogenic (LG) diet for 10 weeks. Dietary garlic and onion reduced the CGS incidence by 15–39 %, the effect being maximum in the heat-processed onion group. Dietary garlic and onion markedly reduced biliary cholesterol. The cholesterol:phospholipid ratio which was 1·58 in the LG diet group was reduced to 0·73–0·96 in the garlic and onion groups. The biliary cholesterol saturation index was 0·92, 1·25, 1·09 and 0·86, respectively, in the heat-processed onion, raw garlic, heat-processed garlic and raw onion groups, while it was 1·9 in the LG group. The hydrophobicity index of bile was − 0·08, − 0·079, − 0·032 and − 0·073, respectively, in the heat-processed onion, raw garlic, heat-processed garlic and raw onion groups, while it was +0·054 in the LG group. Hepatic hydroxymethyl glutaryl-CoA reductase activity was lowered in the LG diet-fed group, while dietary garlic or onion countered this alteration and also increased the activities of hepatic cholesterol 7α-hydroxylase and sterol 27-hydroxylase. Serum and liver cholesterol were decreased by feeding garlic or onion compared to the LG diet. Thus, dietary Allium spices exerted antilithogenic influence by decreasing the cholesterol hyper-secretion into bile and increasing the bile acid output thus decreasing the formation of lithogenic bile in experimental mice.

BMI is commonly used as a sole indicator for the assessment of nutritional status. While it is a good predictor of morbidity and mortality among young and middle-aged adults, its predictive ability among the oldest old remains unclear. The objective of the present study was to investigate the relationship between BMI and risk of falls, fractures and all-cause mortality among older Australians in residential aged care facilities. One thousand eight hundred and forty-six residents of fifty-two nursing homes and thirty hostels in northern Sydney, Australia, participated in the present study. Baseline weight and height were measured and BMI (kg/m2) calculated. For 2 years following the baseline measurements, incidence and date of all falls and fractures were recorded by research nurses who visited the facilities regularly and date of death was documented based on the participants' records at each facility. Cox proportional hazards regression models were calculated to determine the relationship between baseline BMI and time to fall, fracture or death, within 2 years following the baseline measures taken to be the censoring date. After adjustments were made for age, sex and level of care, low BMI ( < 22 kg/m2) increased the risk of fracture by 38 % (hazard ratio = 1·38, 95 % CI 1·11, 1·73) and all-cause mortality by 52 % (hazard ratio = 1·52, 95 % CI 1·30, 1·79). The magnitude of this effect was only slightly reduced when adjustments were further made to incorporate cognition, number of medications, falls and fracture in the subsequent 2-year period. In conclusion, BMI has predictive ability in the area of fracture and all-cause mortality for residents of aged care facilities. It is a simple and rapid indicator of nutritional status rendering it a useful nutrition screen and goal for nutrition intervention.

Integrins are transmembrane proteins that facilitate the interaction of cells with the extracellular environment. They have also been implicated in cancer progression. The effects of nutrients thought to be involved in the prevention of prostate cancer on integrin expression have not been determined. Prostate cancer cell lines representing a range of malignancy from normal (RWPE-1) to highly invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene (10 nm), vitamin E (5 μm) or fish oil (100 μm) for 48 h. Growth and integrin (α2β1, αvβ3 and αvβ5) expression were assessed using Trypan Blue exclusion and monoclonal antibodies combined with flow cytometry. Vitamin E enhanced (P < 0·001) whereas fish oil reduced the growth of all the cell lines tested (P < 0·001). Lycopene had no effect on growth. All the malignant cell lines exhibited lower expression of α2β1 with the addition of lycopene to culture media. Supplemental fish oil reduced α2β1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins αvβ3 and αvβ5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.

Oligosaccharides are present in human milk in large amounts and in a high variety. We have previously shown that these oligosaccharides are strong inhibitors of proliferation and inducers of differentiation in intestinal cell lines. To elucidate the molecular mechanism, we investigated the influence on cell cycle events via flow cytometry and expression levels by using quantitative real-time RT–PCR. Human intestinal cells, i.e. HT-29, HIEC and Caco-2 cells, were exposed to neutral or acidic human milk oligosaccharides. Both fractions induced a concentration-dependent G2/M arrest. Cell cycle analysis for HT-29 revealed 37 % of cells in G1 and 35 % in G2/M (neutral oligosaccharides) and incubation with acidic oligosaccharides led to 42 % cells in G1 and 40 % in G2/M. In control experiments without oligosaccharides we found 71 % of cells to be in G1 and 17 % in G2/M. This G2/M arrest was associated with changes in mRNA expression of cyclin A and B. A G2/M arrest with concomitant alterations of cell cycle gene expression could also be shown for HIEC and Caco-2 cells. Analysing the expression of cyclin-dependent kinase inhibitors p21cip1 and p27kip1 and the tumour suppressor p53 we observed that the expression of p21cip1 was p53-independent and necessary for arresting cells in the G2/M phase, while p27kip1 was associated with differentiation effects. Both neutral and acidic human milk oligosaccharides were able to induce epidermal growth factor receptor, extracellular signal-regulated kinase 1/2 and p38 phosphorylation. These results suggest that oligosaccharides from human milk inhibited intestinal cell proliferation and altered cell cycle dynamics by affecting corresponding regulator genes and mitogen-activated protein kinase signalling.

The effect of processing (homogenization, lyophilization, acid-extraction) meat products on iron uptake from meat combined with uncooked iron-fortified cereal was evaluated using an in vitro digestion/Caco-2 cell model. Beef was cooked, blended to create smaller meat particles, and combined with electrolytic iron-fortified infant rice cereal. Chicken liver was cooked and blended, lyophilized, or acid-extracted, and combined with FeSO4-fortified wheat flour. In the beef–cereal combination, Caco-2 cell iron uptake, assessed by measuring the ferritin formed by cells, was greater when the beef was blended for the greatest amount of time (360 s) compared with 30 s (P < 0·05). Smaller liver particles (blended for 360 s or lyophilized) significantly enhanced iron uptake compared to liver blended for 60 s (P < 0·001) in the liver–flour combination. Compared to liver blended for 60 s, acid-extraction of liver significantly enhanced iron uptake (P = 0·03) in the liver–flour combination. Homogenization of beef and homogenization, lyophilization, or acid-extraction of chicken liver increases the enhancing effect of meat products on iron absorption in iron-fortified cereals.

The susceptibility to develop hepatic steatosis is known to differ between duck species, especially between Muscovy and Pekin ducks. This difference could be explained by either differential responses of species to overfeeding or genetic differences in hepatic lipid metabolism. The aim of the present study was to compare the intensities of the different hepatic pathways (oxidation, lipogenesis, esterification, secretion, etc.) of the two main nutrients (glucose and linoleic acid (LA)) reaching the liver of ad libitum-fed Muscovy (n 6) and Pekin (n 6) ducks using the ex vivo method of liver slices incubated for 16 h with [U-14C]glucose, [1-14C]LA and [35S]methionine added to the survival medium. In such experimental conditions, the lipogenesis pathway from glucose was 2-fold higher (P < 0·05) in the liver of the Muscovy duck than in that of the Pekin duck. Furthermore, the hepatic uptake of LA was 2-fold higher (P < 0·05) in the Muscovy duck than in the Pekin duck leading to a 2-fold higher (P < 0·05) esterification of this fatty acid in the liver of the Muscovy duck. The hepatic secretion of VLDL was higher (P < 0·01) in the Muscovy duck than in the Pekin duck but insufficient to prevent lipid accumulation in the liver of the Muscovy duck. In conclusion, these results show the influence of the species on the hepatic metabolism of ducks in relation to their susceptibility to develop fatty liver. These results should shed light on the metabolic regulations that might underlie susceptibility to hepatic steatosis in the the human liver.

Dietary non-digestible carbohydrates (NDC) play an important role in large-bowel health and one form of NDC, resistant starch (RS), can promote low levels of DNA damage and other markers of colonic health. The objective of the present study was to determine whether the ability of dietary RS or other NDC to influence colonic health, particularly DNA damage, is dependent on the type of dietary oil. We compared the effects of diets containing 10 % of NDC from cellulose, wheat bran, high-amylose maize starch (HAS, a rich source of RS type 2) or a retrograded HAS (RHAS, a rich source of RS type 3) on DNA damage, SCFA production and bacterial changes in the large bowel of rats. Each carbohydrate source was combined with 10 % fish oil (FO) or Sunola™ oil (SO; rich in oleic acid). There was a significant interaction between NDC and oil treatments on single-strand DNA breaks in colonocytes isolated from the colon. The damage in rats consuming RHAS was greater for FO consumption than for SO consumption. There was a significant interaction between NDC and oils on caecum weights and treatment effects of NDC and oils were observed for the weights and lengths of other gut tissues. Significant differences were found in colonic SCFA pools and caecal numbers of lactobacilli, bifidobacteria, Escherichia coli and Bacteroides fragilis with the various NDC and oil treatments. The present results demonstrate that the effects of NDC and oils, particularly on colonic DNA damage, can depend on how they are combined within the diet.

Crude saponins derived from Chinese Platycodi radix have been reported to prevent increases in body weight and liver TAG in mice fed a high-fat diet. We investigated the effects of an extract (PR) taken from Korean Platycodi radix, which is cultivated for 22 years in the ground (Jangsaeng doraji), and its saponins (PRS) on insulin resistance and glucose-stimulated insulin secretion in 90 % pancreatectomized diabetic rats fed high-fat diets. Four groups were orally supplemented with 2 g PR, 0·2 g PRS, 20 mg rosiglitazone (positive control) or 0·5 g cellulose (negative control) per kg body weight on a daily basis for 8 weeks. We found that PRS lowered body weight, visceral fat mass and serum leptin levels in pancreatectomized rats in comparison to the control. PR enhanced first- and second-phase insulin secretion while PRS stimulated only first-phase insulin secretion. Glucose infusion rates to maintain euglycaemia at hyperinsulinaemic states decreased in a descending order of rosiglitazone, PRS, PR and control, but they increased hepatic glucose output in the same order. This reduction was associated with the storage of decreased TAG and increased glycogen, which was a result of enhanced tyrosine phosphorylation of anti-insulin receptor substrate-2 and serine473 phosphporylation of protein kinase B (PKB, Akt). Improved hepatic insulin signalling led to decreased phosphoenolpyruvate carboxykinase expression and reduced hepatic glucose output accordingly. In conclusion, PRS principally improves glucose homeostasis by enhancing hepatic insulin sensitivity as a consequence of reducing fat storage and stimulating insulin signalling in diabetic rats. In addition, PR contains components that promote glucose-stimulated insulin secretion.