Associations of mucosal disaccharidase kinetics and expression in the jejunum of steers with divergent average daily gain.

The objective of this study was to quantify the differences in the activity of jejunal maltase and isomaltase between two groups of steers with average dry matter intake (DMI) and differing average daily gain (ADG). DMI and ADG were measured in crossbred steers (n = 69; initial body weight = 456 ± 5.0 kg) consuming a finishing diet containing 67.8% dry-rolled corn, 20.0% wet distillers grains with solubles, 8.0% alfalfa hay, and 4.2% vitamin/mineral supplement on a dry matter basis for 84 d. Jejunal mucosal samples were collected from eight steers with the greatest (high) or least (low) ADG and average DMI (± 0.55 standard deviation). Homogenates of jejunal mucosa were incubated with increasing amounts of maltose and isomaltose to determine the disaccharidase kinetics. Total mucosal protein concentration (mg protein/g tissue; P = 0.45) of the mucosa and small intestinal weights (P = 0.69) did not differ between the groups. Neither the Michaelis-Menten constant (Km) of isomaltase (P = 0.15) nor maltase (P = 0.21) differed between groups. The isomaltase maximum velocity (Vmax) expressed per gram of protein tended to differ (P = 0.10) between groups of steers but did not differ (P = 0.13) when expressed on a tissue basis. Similarly, neither the maltase Vmax expressed per gram of protein (P = 0.31) nor tissue (P = 0.32) differed between groups. While previous studies have indicated that disaccharidase expression is associated with differences in ADG, data presented here indicate that differences in enzyme activity at the end of the finishing period are minimal.

Mulberry leaf polyphenols attenuated postprandial glucose absorption via inhibition of disaccharidases activity and glucose transport in Caco-2 cells.

The present study attempted to evaluate the mechanism of action and bioactivity of mulberry leaf polyphenols (MLPs) in type-2 diabetes prevention via inhibition of disaccharidase and glucose transport. MLPs were purified with D101 resin and the main composition was determined as chlorogenic acid, rutin, benzoic acid and hyperoside. MLPs demonstrated a strong inhibitory effect on disaccharidases derived from both mouse and Caco-2 cells, and the order of IC50 value was: murine sucrase (7.065 mg mL-1) > murine maltase (4.037 mg mL-1) > Caco-2 cell maltase (0.732 mg mL-1) > Caco-2 cell sucrase (0.146 mg mL-1). MLPs showed the strongest inhibitory effect on sucrase derived from Caco-2 cells and played a role in lowering postprandial glucose mainly by inhibiting sucrase activity. The Caco-2 monolayer cell model was established to simulate the glucose transport process in the human small intestine. We found that within the concentration range of 0.5-2 mg mL-1, MLPs significantly inhibited glucose transport, and the inhibition rate increased with time and dose. The effect of phlorizin (SGLT1 inhibitor) in the control group showed a similar effect on glucose transport, revealing that MLPs may inhibit glucose transport mainly by inhibiting the SGLT1 transporter. RT-qPCR analysis confirmed that MLPs inhibited glucose absorption by suppressing the SGLT1-GLUT2 pathway via downregulation of the mRNA expression of phospholipase, protein kinase A and protein kinase C.

Modulatory effects of Caralluma fimbriata extract against high-fat diet induced abnormalities in carbohydrate metabolism in Wistar rats.

The present study was aimed to evaluate the modulatory effects of hydroalcoholic extract of Caralluma fimbriata (CFE) by assaying the activities of key enzymes of carbohydrate metabolism and changes in glycogen content (liver and muscle) in high-fat (HF) diet-induced diabetic rats. In vitro glucose uptake studies were carried out in both psoas muscle and adipose tissue. The inhibitory effect of the extract on α-amylase was determined in in vitro studies. Male Wistar rats of body weight around 180g were divided into five groups (n=8), two of these groups were fed with standard pellet diet and the other three groups were fed with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of standard pellet diet rats and HF-fed rats and Metformin (Met) (20mg/kg body weight/day) was administered through oral route to HFD+Met group for 90 days. At the end of the experimental period, biochemical parameters related to glycogen content in liver and muscle, and intestinal disaccharidases like maltase, sucrase and lactase were assayed. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphorfructoki nase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase), intestinal disaccharidases and glycogen content as observed in the high fat diet-fed rats were prevented with CFE/Met administration. From this study, we observed that CFE/Met could significantly restore the levels of glycogen in liver and muscle and key enzymes of carbohydrate metabolism to near normal in groups-HFD+CFE and HFD+Met. The skeletal muscle of HF-diet fed rats showed degenerative changes of muscle myofibers with fat deposition. These changes were attenuated in the HFD group treated with CFE/Met and retained their normal structure appearance. It can be concluded from these results that CFE might be of value in reducing the alterations related to carbohydrate metabolism under high calorie diet consumption.

Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs.

This study was conducted to explore whether exposure to bisphenol A (BPA) during pregnancy could change intestinal digestion and absorption function in offspring using pigs as a model, and whether methyl donor (MET) could counteract the BPA-induced impacts. Fifty Landrace × Yorkshire sows were divided into four dietary groups throughout gestation: control diet (CON); control diet supplemented with BPA (50 mg/kg); control diet supplemented with MET (3 g/kg betaine, 400 mg/kg choline, 150 µg/kg vitamin B12, and 15 mg/kg folic acid); and control diet with BPA and MET supplementation (BPA + MET). Intestine samples were collected from pigs' offspring at birth and weaning. Maternal BPA exposure during pregnancy significantly reduced the ratio of jejunum villus height to crypt depth, decreased the jejunum sucrase activity, down-regulated the mRNA expression of jejunum peptide transporter 1 (Pept1) and DNA methyl transferase 3a (DNMT3a), and decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). Maternal MET supplementation significantly raised the ratio of villus height to crypt depth in jejunum and ileum, improved the jejunum lactase activity, up-regulated the mRNA expression of jejunum Pept1, lactase (LCT), DNMT1, DNMT3a, and methylenetetrahydrofolate reductase (MTHFR), and increased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). However, the ratio of jejunum villus height to crypt depth was higher in BPA + MET treatment compared with CON and BPA treatment (p < 0.05). Meanwhile, there was no difference in the jejunum sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA methylation level of jejunum Pept1 between CON and BPA + MET treatment. These results indicated that maternal exposure to BPA during gestation might suppress offspring's intestinal digestion and absorption function, whereas supplementation of MET could counteract these damages, which might be associated with DNA methylation.

Asparagine attenuates intestinal injury, improves energy status and inhibits AMP-activated protein kinase signalling pathways in weaned piglets challenged with Escherichia coli lipopolysaccharide.

The intestine requires a high amount of energy to maintain its health and function; thus, energy deficits in intestinal mucosa may lead to intestinal damage. Asparagine (Asn) is a precursor for many other amino acids such as aspartate, glutamine and glutamate, which can be used to supply energy to enterocytes. In the present study, we hypothesise that dietary supplementation of Asn could alleviate bacterial lipopolysaccharide (LPS)-induced intestinal injury via improvement of intestinal energy status. A total of twenty-four weaned piglets were assigned to one of four treatments: (1) non-challenged control; (2) LPS+0 % Asn; (3) LPS+0·5 % Asn; (4) LPS+1·0 % Asn. On day 19, piglets were injected with LPS or saline. At 24 h post-injection, piglets were slaughtered and intestinal samples were collected. Asn supplementation improved intestinal morphology, indicated by higher villus height and villus height:crypt depth ratio, and lower crypt depth. Asn supplementation also increased the ratios of RNA:DNA and protein:DNA as well as disaccharidase activities in intestinal mucosa. In addition, Asn supplementation attenuated bacterial LPS-induced intestinal energy deficits, indicated by increased ATP and adenylate energy charge levels, and decreased AMP:ATP ratio. Moreover, Asn administration increased the activities of key enzymes involved in the tricarboxylic acid cycle, including citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase complex. Finally, Asn administration decreased the mRNA abundance of intestinal AMP-activated protein kinase-α1 (AMPKα1), AMPKα2, silent information regulator 1 (SIRT1) and PPARγ coactivator-1α (PGC1α), and reduced intestinal AMPKα phosphorylation. Collectively, these results indicate that Asn supplementation alleviates bacterial LPS-induced intestinal injury by modulating the AMPK signalling pathway and improving energy status.

The ethanol extract of Eucommia ulmoides Oliv. leaves inhibits disaccharidase and glucose transport in Caco-2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The cortex and leaves of Eucommia ulmoides Oliv. from the family Eucommiaceae are traditional Chinese medicines (TCM). Roasted Eucommiae cortex is utilized to reinforce the muscles and lungs, lower blood pressure and improve the tone of the liver and kidneys, while Eucommia ulmoides leaves (EUL) are traditionally used as folk remedies to treat diabetes. MATERIALS AND METHODS: EUL extract, obtained by ethanol (40%) was loaded onto an AB-8 macroporous resin column, and washed thoroughly with 0, 20, 40, 60, and 80% (v/v) ethanol for purification. The ethanol eluents of EUL were first determined to inhibit α-glucosidase in vitro, and then the inhibition of the most potent eluent, i.e., 20% ethanol eluent of EUL (EEUL), against carbohydrate-degrading enzymes and glucose transport in Caco-2 cells was demonstrated. And computational modeling was also employed to evaluate the binding modes of compounds identified in EEUL by GC-MS analysis. RESULTS: EEUL significantly inhibited α-glucosidase (43.08±0.55%) competitively in vitro and concentration-dependently suppressed sucrase (IC50, 0.07mg/mL) and maltase (IC50, 0.53mg/mL) in Caco-2 cells. The inhibitory activity of EEUL (0.02mg/mL) on sucrase and maltase was identical to that of acarbose (0.02mg/mL). Moreover, 1.0mg/mL EEUL decreased glucose transport in cells by 26.25±0.86%. GC-MS revealed that EEUL was rich in monosaccharides, polyphenols and esters, which comprised 47.16% of the total extract. Computational modeling showed that catechin, α-d-glucopyranose and d-mannono-1,4-lactone docked tightly into the sucrase active site with low binding energies. CONCLUSION: These results indicated that EEUL exerted marked anti-hyperglycemic effects by suppressing disaccharidases and glucose transporters. Therefore, EUL is a beneficial source of inhibitors of carbohydrate-utilizing enzymes, glucose transporters, and potentially hyperglycemia.

Long term differential consequences of miglustat therapy on intestinal disaccharidases.

Miglustat is an oral medication for treatment of lysosomal storage diseases such as Gaucher disease type I and Niemann Pick disease type C. In many cases application of Miglustat is associated with symptoms similar to those observed in intestinal carbohydrate malabsorption. Previously, we have demonstrated that intestinal disaccharidases are inhibited immediately by Miglustat in the intestinal lumen. Nevertheless, the multiple functions of Miglustat hypothesize long term effects of Miglustat on intracellular mechanisms, including glycosylation, maturation and trafficking of the intestinal disaccharidases. Our data show that a major long term effect of Miglustat is its interference with N-glycosylation of the proteins in the ER leading to a delay in the trafficking of sucrase-isomaltase. Also association with lipid rafts and plausibly apical targeting of this protein is partly affected in the presence of Miglustat. More drastic is the effect of Miglustat on lactase-phlorizin hydrolase which is partially blocked intracellularly. The de novo synthesized SI and LPH in the presence of Miglustat show reduced functional efficiencies according to altered posttranslational processing of these proteins. However, at physiological concentrations of Miglustat (≤50 µM) a major part of the activity of these disaccharidases is found to be still preserved, which puts the charge of the observed carbohydrate maldigestion mostly on the direct inhibition of disaccharidases in the intestinal lumen by Miglustat as the immediate side effect.

Characterization of nimbidiol as a potent intestinal disaccharidase and glucoamylase inhibitor present in Azadirachta indica (neem) useful for the treatment of diabetes.

Azadirachta indica, used in antidiabetic herbal drugs, was reported to contain α-glucosidase inhibitor. Bioassay guided purification characterized the inhibitor as nimbidiol (a diterpenoid), present in root and stem-bark of the tree. Nimbidiol inhibited intestinal (mammalian) maltase-glucoamylase, sucrase-isomaltase, lactase, trehalase and fungal α-glucosidases. Nimbidiol showed a mixed competitive inhibition on intestinal carbohydrases. IC50, Ki and Ki' (µM) were 1.35 ± 0.12, 0.08 ± 0.01, 0.25 ± 0.11, respectively, for maltase-glucoamylase (maltotetraose as substrate). Nimbidiol was more potent inhibitor of isomaltase (IC50 0.85 ± 0.035 µM), lactase (IC50 20 ± 1.33 µM) and trehalase (IC50 30 ± 1.75 µM) than acarbose, voglibose, salacinol, kotalanol and mangiferin. Ki and Ki' values (µM) for intestinal sucrase were 0.7 ± 0.12 and 1.44 ± 0.65, respectively. Development of nimbidiol as an antidiabetic drug appears to be promising because of broad inhibition spectrum of intestinal glucosidases and easy synthesis of the molecule.

Possible effects of dietary polyphenols on sugar absorption and digestion.

Excessive post-prandial glucose excursions are a risk factor for developing diabetes, associated with impaired glucose tolerance. One way to limit the excursion is to inhibit the activity of digestive enzymes for glucose production and of the transporters responsible for glucose absorption. Flavonols, theaflavins, gallate esters, 5-caffeoylqunic acid and proanthocyanidins inhibit α-amylase activity. Anthocyanidins and catechin oxidation products, such as theaflavins and theasinsensins, inhibit maltase; sucrase is less strongly inhibited but anthocyanidins seem somewhat effective. Lactase is inhibited by green tea catechins. Once produced in the gut by digestion, glucose is absorbed by SGLT1 and GLUT2 transporters, inhibited by flavonols and flavonol glycosides, phlorizin and green tea catechins. These in vitro data are supported by oral glucose tolerance tests on animals, and by a limited number of human intervention studies on polyphenol-rich foods. Acarbose is a drug whose mechanism of action is only through inhibition of α-amylases and α-glucosidases, and in intervention studies gives a 6% reduction in diabetes risk over 3 years. A lifetime intake of dietary polyphenols, assuming the same mechanism, has therefore a comparable potential to reduce diabetes risk, but more in vivo studies are required to fully test the effect of modulating post-prandial blood glucose in humans.

Influence of the traditional Brazilian drink Ilex paraguariensis tea on glucose homeostasis.

In this study we examined the acute in vivo effect and short- and long-term in vitro effects of samples from native and commercial Ilex paraguariensis on glucose homeostasis. Also, the potential effect of I. paraguariensis on serum insulin secretion was investigated. The chemical identification and quantification of methyl xanthines and polyphenols in CH2Cl2, EtOAc and n-BuOH fractions of native I. paraguariensis as well as infusions of green and roasted I. paraguariensis from a commercial source was verified by high-performance liquid chromatography. The results for the serum glucose-lowering indicated that both fractions and both infusions were able to improve significantly the oral glucose tolerance curve. Additionally, both the EtOAc and n-BuOH fractions induced-insulin secretion, but EtOAc induced an early (at 15 min) and late (at 60 min) biphasic peak of insulin secretion similar to glipizide stimulatory effect. Both fractions increased liver glycogen content compared with fasted normal rats. Also, EtOAc and n-BuOH fractions inhibited in vitro disaccharidases activities after an acute treatment. The maximum inhibitory effect of the EtOAc and n-BuOH fractions on maltase activity (at 5 min) was around 35%. The evident reduction of protein glycation by glucose or fructose with EtOAc and n-BuOH fractions increased from 7 to 28 days of in vitro incubation. Inhibition of bovine serum albumin glycation by glucose and fructose, by around 50% and 90%, respectively, was observed. Additionally, the green and roasted mate infusions reduced the formation of AGEs in a characteristic long-term effect. In conclusion, this study shows that I. paraguariensis has an anti-hyperglycemic potential role able to improve the diabetic status and is probably a source of multiple hypoglycemic compounds.

In vitro ¹4C-labeled amino acid uptake changes and surface abnormalities in the colon after 1,2-dimethylhydrazine-induced experimental carcinogenesis: protection by zinc.

The present study explored the regulatory role of zinc on the in vitro uptake of ¹4C-glucose and ¹4C-labeled amino acids and on colonic surface abnormalities after 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: control, DMH-treated, zinc-treated, and DMH + zinc-treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Zinc (in the form of zinc sulfate) was given to rats at a dose level of 227 mg/L in their drinking water. DMH treatment caused a significant decrease in the activities of disaccharidases (sucrase, lactase, and maltase), but a significant increase in the activity of alkaline phosphatase. In vitro uptake of ¹4C-D-glucose and the amino acids ¹4C-glycine, ¹4C-alanine, ¹4C-lysine, and ¹4C-leucine were significantly higher in the colons of DMH-treated rats. Zinc supplementation of DMH-treated rats resulted in regulating the altered intestinal enzyme activities and in vitro uptake of ¹4C-amino acids and ¹4C-glucose. Scanning electron microscopy revealed drastic alterations in the colon surface morphology after DMH treatment, which were restored after zinc supplementation. Our results confirm a beneficial effect of zinc against DMH-induced alterations in the colons of rats.

Polysaccharide from Gynura divaricata modulates the activities of intestinal disaccharidases in streptozotocin-induced diabetic rats.

During diabetes, structural and functional changes in the alimentary tract are known to take place resulting in an increased absorption of intestinal glucose and alterations in the activities of brush-border disaccharidases. To elucidate the effect of administrating polysaccharide from Gynura divaricata (PGD) on disaccharidase activities, the specific activities of intestinal disaccharidases, namely sucrase, maltase and lactase, were measured in streptozotocin-induced diabetic rats. Normal control and diabetic rats were treated by oral administration with PGD. Specific activities of intestinal disaccharidases were increased significantly during diabetes, and amelioration of the activities of sucrase and maltase during diabetes was clearly visible by the treatment with PGD. However, the increased activity of lactase during diabetes mellitus was remarkably alleviated by the administration of PGD only in the duodenum. Meanwhile, oral sucrose tolerance tests demonstrated that PGD alleviated the hyperglycaemia during diabetes mellitus, resulting from the amelioration in the activities of intestinal disaccharidases. The present investigation suggests that PGD exerted an anti-diabetic effect partly via inhibiting the increased intestinal disaccharidase activities of diabetic rats. This beneficial influence of administration of PGD on intestinal disaccharidases clearly indicates their helpful role in the management of diabetes.

Evaluation of the marine alga Ulva rigida as a food supplement: effect of intake on intestinal, hepatic, and renal enzyme activities in rats.

The use of seaweeds as a food is more widespread in Eastern than in Western countries, although demand for these plants has increased in the West because their possible usefulness as dietary supplements. However, very little is known about the effects of regular consumption of algae. The aim of the present study was to determine the composition of Ulva rigida and to evaluate the effects of dietary supplementation of the diet with 10% alga for 4 weeks on dietary intake, growth, protein efficiency ratio, diet conversion ratio, and some organ weights in growing male rats. We also studied the effect of inclusion of the alga in the diet on intestinal, hepatic, and renal enzymatic activities. U. rigida was found to be a good source of protein and carbohydrates. Food intake was higher in the U. rigida group than in the control group, but ingestion of alga did not have any effect on the other trophic parameters. The intestinal disaccharidase and leucine aminopeptidase activities were lower in rats fed with alga than in control rats, but γ-glutamyl transpeptidase activity was higher in the kidneys of alga-fed rats than in control rats. U. rigida contains high amounts of protein, carbohydrates, vitamins, and minerals and low amounts of lipids. Analysis of the amino acid composition revealed good-quality protein. The addition of alga to the diet inhibited disaccharidase activities, which suggested that alga consumption could be useful in some chronic disorders associated with pertubations of glucose homeostasis caused by carbohydrate absorption.

[Effect of Weichang'an pill on intestinal digestion enzymes and the AQP4 concentration in proximal colon in IBS-D rats].

OBJECTIVE: To investigate the influence of Weichang'an pill on the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in model rats. METHOD: Animal model of compound diarrhea was induced by a lactose enriched diet in the Wistar rat, combining with restraint stress. Twenty four female Wistar rats were randomly divided into normal group, model group and 60 mg x kg(-1) x d(-1) Weichang'an pill group. The rate of weight increase, the incubation period of diarrhea and the diarrhea index were observed. Then 45 female Wistar rats randomly divided into five groups: control group, model group and Weichang'an pill groups of high, medium and low doses (80, 60, 40 mg x kg(-1) x d(-1)). The indexes of thymus and spleen were calculated. The activities of LDH, MDH and disaccharidase in intestinal organization were inspected. Serum D-xylose content and the AQP4 concentration in proximal colon were detected. RESULT: After taking Weichang'an pill for 4 days, the rate of weight increase in Weichang'an pill group was higher than the model group's. While the rate of diarrhea was lower significantly. So the best cycle of taking medicine was 4 days. The indexes of thymus and spleen of model group were decreased than that of control group. And the activities of LDH, MDH and disaccharidase in intestinal organization were also decreased. But the AQP4 concentration in proximal colon was increased. Compared with the model group, the indexes of thymus and spleen increased remarkably in the group of medium doses. Meanwhile, the activities of LDH, MDH and disaccharidase increased. But the AQP4 concentration didn't change. CONCLUSION: Weichang'an pill has the effect of antidiarrhea. It can adjust the sugar's catabolism through increasing the activity of intestinal digestive ferment.

Immobilization of flavonol 3-O-beta-heterodisaccharidase on porous glass and production of rutinose from rutin.

Flavonol 3- O-beta-heterodisaccharidase (FHG 1) was isolated from the dried herb of Fagopyrum esculentum, immobilized on porous glass, and used for the release of rutinose from rutin. The stability of the enzyme in its free or immobilized form was observed continuously at two different temperatures (4 degrees C and 25 degrees C). T(1/2) values were determined to be about 48 h for the free enzyme and about 300 h for the immobilized enzyme. The rutinose released was isolated by fractionated ethanol precipitation.

Ingestion of black chokeberry fruit extract leads to intestinal and systemic changes in a rat model of prediabetes and hyperlipidemia.

This report presents a complex analysis of changes proceeding in the gut, blood and internal organs of rats with induced oxidative stress, glucose intolerance and hyperlipidemia after dietary supplementation with an extract from black chokeberry (Aronia melanocarpa) fruit, that is a condensed source of polyphenols (714 mg/g), especially anthocyanin glycosides (56.6%). The disturbances mimicking those observed in metabolic syndrome were induced by a high-fructose diet and simultaneous single injection of streptozotocin (20 mg/kg). Dietary supplementation with the chokeberry fruit extract (0.2%) decreased activity of maltase and sucrase as well as increased activity of lactase in the mucosa of the small intestine. Its ingestion led also to the improvement of antioxidant status, especially, the concentration of a lipid peroxidation indicator (TBARS) in organ tissues (liver, kidney and lung) was normalized; some cholesterol-lowering and distinct hypoglycemic actions were also observed. The mechanism of glucose reduction is likely to be multifactorial, and we suggest the factors related with the decreased activity of mucosal disaccharidases important for further investigation. In conclusion, chokeberry fruit derivatives may act as a promising supplementary therapeutic option in the prevention and treatment of disorders occurring in metabolic syndrome, as well as their complications.

Inhibidores de las disacaridasas / Disaccharide inhibitors

La acarbosa es el inhibidor de las alfaglucosidasas más conocido en el tratamiento de la diabetes tipo 2. Al inhibir estas enzimas, se logra retardar la hidrólisis de los hidratos de carbono de cadena larga y con ello se alcanza una reducción de los picos posprandiales de glucosa. Este efecto provoca una reducción de las cifras de hemoglobina glucadaentre un 0,7-1%. No produce episodios de hipoglucemia. Los efectos secundarios más destacados son flatulencia, meteorismo y, en casos esporádicos, diarreas. Está indicada como tratamiento antidiabético oral asociado a cambios en el estilo de vida, así como en combinación con otros agentes orales –metformina, glitazonas y sulfonilureas– y con insulina. Recientemente, se ha utilizado en prevención de la diabetes tipo 2 en la población con riesgo de padecerla (intolerantes a la glucosa).Los resultados han indicado que es capaz de retrasar la aparición de la enfermedad y, a su vez, de reducir el número de episodios cardiovasculares, en especial el infarto de miocardio (AU)

Acarbose in the best knownalpha-glucosidase inhibitor in the treatment of type 2 diabetes. By inhibiting these enzymes, hydrolysis of long-chain carbohydrates is delayed, thus reducing postprandial glucose peaks. This effect reduces glycosylated hemoglobin levels by 0.7-1% and does not produce hypoglycemic episodes. The most important adverse effects are flatulence, tympanites and, in sporadic cases, diarrhea. Acarbose is indicated as an oral anti-diabetic agent associated with lifestyle changes, as well as in combination with other oral agents–metformin, glitazones and sulfonylureas–and with insulin. Recently, acarbose has been used in the population at risk of developing type 2 diabetes (glucose intolerance). The results have indicated that this drug is able to delay the onset of the disease and, in turn, to reduce the number of cardiovascular events, especially myocardial infarction (AU)

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on intestinal function in streptozotocin-induced diabetic rats.

We examined the effects of Hachimi-jio-gan (HJ) on the small intestinal function in streptozotocin (STZ)-induced diabetic rats. The rats had free access to pellets containing 1% HJ extract powder for 4 weeks after STZ administration. The intestinal disaccharidase (sucrase and maltase) activity was elevated in STZ-treated rats compared with control rats, whereas it was significantly reduced by HJ administration. This suggested that HJ suppresses or delays monosaccharide production in the small intestinal epithelium. In addition, the intestinal mucosal weights and DNA contents that were significantly increased in the STZ-treated rats were restrained to the control level by HJ treatment. Simultaneously, we examined the changes in the plasma levels of glucagon-like peptide 2 (GLP-2), which is a trophic factor specific for the intestine. The plasma GLP-2 levels significantly increased in the STZ-treated rats, whereas HJ decreased the plasma GLP-2 levels. Thus intestinal mucosal weights and DNA contents correlated with plasma GLP-2 levels in diabetes-associated bowel growth. These results suggest that HJ may normalize or suppress the small intestinal disaccharidase activity and the epithelial cell proliferation mediated by GLP-2 in the animal model rats.

Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action.

Trigonella foenum-graecum (fenugreek) seeds have been documented as a traditional plant treatment for diabetes. In the present study, the antidiabetic properties of a soluble dietary fibre (SDF) fraction of T. foenum-graecum were evaluated. Administration of SDF fraction (0 x 5 g/kg body weight) to normal, type 1 or type 2 diabetic rats significantly improved oral glucose tolerance. Total remaining unabsorbed sucrose in the gastrointestinal tract of non-diabetic and type 2 diabetic rats, following oral sucrose loading (2 x 5 g/kg body weight) was significantly increased by T. foenum-graecum (0 x 5 g/kg body weight). The SDF fraction suppressed the elevation of blood glucose after oral sucrose ingestion in both non-diabetic and type 2 diabetic rats. Intestinal disaccharidase activity and glucose absorption were decreased and gastrointestinal motility increased by the SDF fraction. Daily oral administration of SDF to type 2 diabetic rats for 28 d decreased serum glucose, increased liver glycogen content and enhanced total antioxidant status. Serum insulin and insulin secretion were not affected by the SDF fraction. Glucose transport in 3T3-L1 adipocytes and insulin action were increased by T. foenum-graecum. The present findings indicate that the SDF fraction of T. foenum-graecum seeds exerts antidiabetic effects mediated through inhibition of carbohydrate digestion and absorption, and enhancement of peripheral insulin action.

Aqueous extracts of husks of Plantago ovata reduce hyperglycaemia in type 1 and type 2 diabetes by inhibition of intestinal glucose absorption.

Plantago ovata has been reported to reduce postprandial glucose concentrations in diabetic patients. In the present study, the efficacy and possible modes of action of hot-water extracts of husk of P. ovata were evaluated. The administration of P. ovata (0.5 g/kg body weight) significantly improved glucose tolerance in normal, type 1 and type 2 diabetic rat models. When the extract was administered orally with sucrose solution, it suppressed postprandial blood glucose and retarded small intestinal absorption without inducing the influx of sucrose into the large intestine. The extract significantly reduced glucose absorption in the gut during in situ perfusion of small intestine in non-diabetic rats. In 28 d chronic feeding studies in type 2 diabetic rat models, the extract reduced serum atherogenic lipids and NEFA but had no effect on plasma insulin and total antioxidant status. No effect of the extract was evident on intestinal disaccharidase activity. Furthermore, the extract did not stimulate insulin secretion in perfused rat pancreas, isolated rat islets or clonal beta cells. Neither did the extract affect glucose transport in 3T3 adipocytes. In conclusion, aqueous extracts of P. ovata reduce hyperglycaemia in diabetes via inhibition of intestinal glucose absorption and enhancement of motility. These attributes indicate that P. ovata may be a useful source of active components to provide new opportunities for diabetes therapy.