Oral Tolerance Test Research Articles

ラットにおける食後の血糖値に及ぼすコーヒー豆の熱水抽出物の影響

The inhibitory effects were examined of a hot-water extract of coffee beans on Kud: Wistar rats by an in vivo oral saccharinity tolerance test (OST), and the in vitro suppression of alpha-amylase and alpha-glucosidase activity. The hot-water extract of coffee beans strongly inhibited the activities of alpha-amylase and alpha-glucosidase, and reduced the postprandial blood glucose concentration by OST. Chlorogenic acid and acarbose strongly inhibited the activity of alpha-glucosidase, and reduced the postprandial blood glucose concentration by OST. However, caffeine, which is a major component of coffee beans, had no such effect. These results suggest that the inhibitory effect of the hot-water extract of coffee beans on postprandial hyperglycemia may have been due in part to the inhibition of alpha-glucosidase by chlorogenic acid which is a major component of coffee beans.

α‐ガラクトシル基を含むオリゴ糖の合成とその機能

Oligosaccharides with α-D-galactosidic linkages, especially the positional isomers of α-galactobiose (α-Gal 2), participate in such biological processes as immunity and pathogen-to-cell adhesion on the basis of molecular mechanisms for ligand-receptor interaction. α-Linked galactooligosaccharide (α-GOS) containing positional isomers of α-Gal 2 produced from galactose by the reverse reaction of α-galactosidase, is a potential food for the prevention of infections by pathogens, neutralization of toxins, and regulation of immune system. α-GOS (7.5 kg) was produced from galactose (18 kg; prepared from lactose hydrolyzate) by the reverse reaction of α-galactosidase from Aspergillus niger APC-9319. α-GOS contained 58% disaccharide, 28% trisaccharide and 14% oligosaccharides larger than trisaccharide. The disaccharide in α-GOS consisted largely of α-1,6-galactobiose (73%). α-GOS was stable at neutral and acidic pHs, and high temperatures. The sweetness of α-GOS was 25% of that of sucrose. The taste of α-GOS was mild and mellow. α-GOS reduced acid taste, bitterness, astringency, and harsh taste without spoiling the original taste in various fruit juices, and emphasized the original flavor of food materials in various cooked foods. α-GOS was not hydrolyzed in an in vitro digestion method. In oral tolerance tests of α-GOS, the blood glucose level did not change at all. α-GOS had a strong selective growth activity for Bifidobacterium sp. and Clostridium butyricum. An α-GOS intake in rats made the contents of lactate and n-butyrate in the cecum higher, and pH in the cecum lower than for a control intake. The viable count of Candida albicans in cecum and colon of mouse was decreased by an α-GOS intake more than by a raffinose intake. Therapeutic oral treatment with α-GOS had a potent inhibitory effect on adjuvant arthritis in Wister rats and on type II collagen-induced arthritis in DBA/1 J mice. Dietary α-GOS ameliorated allergic airway eosinophilia at least partly via post-absorptive mechanisms in Brown Norway rats.

The absorption of iron bisglycinate (IBC) and ferrus calcium citrate (ICC) is equal using an iron oral tolerance test

The absorption of iron bisglycinate (IBC) and ferrus calcium citrate (ICC) is equal using an iron oral tolerance test

Insulinoma accompanied by diabetes mellitus

A 53-year-old type 2 diabetic man was admitted due to spontaneous relatively hyperinsulinemic hypoglycemia. Oral glucose ingestion and arginine tolerance test showed hyperinsulinemic response. Arterial stimulation and venous sampling (ASVS) showed hyperinsulinemic response measured from the splenic artery after calcium gluconate stimulation. Diagnosis was insulinoma in the pancreas feeding from the artery. He has not suffered from spontaneous hypoglycemia since removal of the pancreatic body, tail and spleen. The specimen showed a solitary islet cell tumor. The high homeostasis model assessment of insulin resistance (HOMA-R) levels reflecting insulin resistance and hyperinsulinemic response after operation remained almost unchanged, indicating high insulin resistance and an insulin hypersecreting diabetic patient.

Targeted disruption of the trehalase gene: determination of the digestion and absorption of trehalose in trehalase-deficient mice

Trehalose has been shown to inhibit bone loss in ovariectomized (OVX) female mice and excessive osteoclastogenesis in lipopolysaccharide (LPS)-injected mice. These facts suggest that there may be select physiological functions for trehalose. Since orally administrated trehalose is digested to glucose by a specific digestive enzyme, trehalase, trehalase-free experimental animals are necessary to study the physiological roles of trehalose in detail. Therefore, we generated trehalase-deficient (treh −/−) mice using the gene-targeting procedure, and an oral trehalose tolerance test revealed that while the blood glucose level increased rapidly in wild-type mice, it was unchanged in treh −/− mice. Thus, these results demonstrate that there is no alternative enzyme for trehalase and suggest that the treh −/− mice are a useful tool to analyze mechanisms of trehalose action on osteoclastogenesis, and the physiological functions of trehalose and trehalase.

Zinc pharmacokinetics in insulin-dependent diabetes mellitus patients after oral zinc tolerance test

Zinc is an essential micronutrient that is directly involved in the physiology of insulin, and zinc metabolism could play a role in the pathogenesis of diabetes mellitus and its complications. On the other hand, low zinc absorption and hyperzincuria in diabetic animals and humans have indicated that diabetics are more susceptible to zinc deficiency. This study was designed to compare zinc metabolism in ten insulin-dependent diabetic patients with ten healthy controls, using an oral zinc tolerance test. Pharmacokinetic parameters were performed to study intestinal zinc absorption and urinary zinc excretion. Absorption of zinc was extensive during the first two hours after administration of a single oral dose of 25 mg Zn ++. The area under the serum zinc curve (AUC) and maximum concentration of zinc (C max) did not differ in both control and experimental groups, p < 0.05. In addition, absorption rate constant (K a), elimination rate constant (K el), absorption half-life (T 1/2a), elimination half-life (T 1/2el), and time of maximum concentration (T max) were not significantly different between the diabetic patients and controls ( p > 0.05). All these kinetic parameters suggest that there is no malabsorption of zinc in diabetic patients. Conversely, zinc clearance/creatinine clearance ratio (CZn ++/Ccr ratio) in diabetic patients differed significantly in comparison to controls, p < 0.05, indicating renal dysfunction in these patients. We conclude that a single oral dose of zinc can be used to investigate zinc absorption and zinc clearance, and that diabetic patients have a specific normal gastrointestinal function and renal dysfunction in terms of zinc clearance.

Chylomicron remnant concentrations in patients with coronary artery disease.

Persisting chylomicron remnants have been linked to premature atherosclerosis. The analysis of chylomicron remnant concentrations by an oral triglyceride tolerance test, however, is time-consuming for the study subjects and requires large resources in the laboratory. Therefore, only small numbers of subjects have been studied in the past. The aim of this study was to elucidate the prevalence of elevated chylomicron remnants, to identify effectors of chylomicron remnant clearance and to compare chylomicron remnants in the prediction of coronary artery disease with other risk factors. We applied a novel oral triglyceride tolerance test to 423 patients (368 males, 55 females) with a confirmed diagnosis of coronary artery disease (CAD) and to 390 control subjects (295 males, 95 females) in a case-control setting. This study revealed that elevated chylomicron remnant concentrations (retinyl esters > 1.5 micromol/l) are present in 20% of all subjects. Male gender, the apolipoprotein E2 isoform, and higher body mass index were associated with increased chylomicron remnant concentrations. However, chylomicron remnants were lower and plasma triglycerides higher in patients with CAD. We conclude that screening for a delayed clearance of chylomicron remnants is of little clinical value in CAD.

Intestinal glucose transport: Evidence for a membrane traffic–based pathway in humans

Background & Aims: The presence of glucose transporter 2 (GLUT2) molecules in the basolateral membrane of enterocytes has long been considered to be of major importance for intestinal glucose absorption. The aim of this study was to reevaluate the role of GLUT2 in a patient with congenital GLUT2 deficiency (Fanconi-Bickel syndrome, FBS). Methods: Oral mono- and disaccharide tolerance tests including gaschromatographic determination of breath hydrogen concentrations were performed in an FBS patient. For comparison, a patient with a microsomal carbohydrate transport defect, glucose-6-phosphate translocase 1 (G6PT1) deficiency, and a control individual were investigated. Results: No increase in breath hydrogen concentration was found in the GLUT2-deficient patient after a glucose load. In G6PT1 deficiency, basal hydrogen concentrations were repeatedly found to be elevated. Conclusions: From the fact that a GLUT2-deficient patient does not show any impairment of intestinal monosaccharide transport measurable by the hydrogen breath test, we conclude that mechanisms other than facilitative glucose transport by GLUT2 must be involved in the transport of monosaccharides at the basolateral membrane of enterocytes. When relating this observation to the high intestinal expression of human hexokinase, G6PT1, and glucose-6-phosphatase and to our results of oral carbohydrate tolerance tests in a G6PT1-deficient patient, there is evidence that a microsomal membrane traffic-based transport pathway, as recently suggested for GLUT2-deficient animals, also plays a major role in transcellular monosaccharide transport of the human intestine.GASTROENTEROLOGY 2003;124:34-39

Single-Dose Oral Tolerance Test with Alternative Compounds for the Management of Adverse Reactions to Drugs

Background: Adverse reactions to drugs are common in the clinical practice. Many outpatients are frequently referred to allergists in order to determine which drugs they can safely take in the future. Objective: We set up an oral single-dose tolerance test procedure to find out for each patient one or more alternative drugs that can be taken when needed. Methods: 452 outpatients (130 male, 322 female) with well-documented reactions (urticaria/angioedema, respiratory symptoms, laryngeal edema, anaphylaxis, exfoliative skin diseases) underwent the challenge. All tests were preceded by a single-blind placebo: if a reaction occurred, a second placebo was administered. Otherwise, a single dose (1/10 of the therapeutic one) of an alternative drug was given blindly and the patient was then observed for 6 h. The drugs used were different in structure from those suspected of having caused the adverse reaction. The patients were followed up at 4- to 6-month intervals, in order to detect any reaction that may have occurred with the tested drugs. Results: 98 patients (89 women) had untoward reactions after the first placebo and 34 out of them reacted to the second placebo, too. During challenges the reaction rate ranged between 4.6 and 9.0%; these reactions were easily managed and none of them was severe. We followed up 407 patients: 87.2% of them were able to use one or more of the suggested drugs without reactions, 9.3% did not take the drugs and only 3.5% reported reactions to the previously tested drugs. Conclusion: The challenge procedure proved to be a simple tool for managing patients with adverse reactions to drugs. Its safety and reliability were validated by a long-term follow-up.

Saponins from Platycodi Radix Ameliorate High Fat Diet–Induced Obesity in Mice

We examined the effects of crude saponins isolated from Platycodi radix on the degree on fat storage induced in mice by feeding a high fat diet for 9 wk. We reported previously that feeding mice a high fat diet for a longer time caused obesity and fatty liver compared with those fed a low fat diet, nonpurified diet. Feeding a high fat diet containing 10 or 30 g/kg crude saponins prevented the body and parametrial adipose tissue weight increases and hepatic steatosis of mice fed the high fat diet alone. Furthermore, crude saponins (375 mg/kg) inhibited the elevations in blood triacylglycerol in rats orally administered a lipid emulsion compared with that of rats given the lipid emulsion alone. Previously, we reported that crude saponins inhibited pancreatic lipase activity in vitro. To identify the active substance(s) of crude saponins, we examined the effects of purified platycodin D, the primary saponin in the crude mixture, on pancreatic lipase activity and on the blood triacylglycerol elevation in rats administered the oral lipid emulsion tolerance test. Platycodin D (0.5 and 1.0 g/L) inhibited pancreatic lipase activity in vitro and at a dose of 244 mg/kg, inhibited the elevation of blood triacylglycerol. Therefore, the antiobesity effect of the crude saponins in mice fed a high fat diet may be due to the inhibition of intestinal absorption of dietary fat by platycodin D.

Perfil hormonal e metabólico em pacientes hirsutas com a síndrome dos ovários policísticos

A síndrome dos ovários policísticos (PCOS) tem sido associada à resistência insulínica/hiperinsulinemia compensatória e a uma maior prevalência de intolerância aos carboidratos (ICH) e diabetes mellitus tipo 2 (DM2). Há controvérsia na literatura sobre se a hiperinsulinemia, presente nas pacientes com PCOS, é independente ou não da obesidade. No presente estudo, avaliaram-se as características hormonais e o perfil metabólico glico-insulínico e lipídico em mulheres hirsutas com o diagnóstico de PCOS em comparação com pacientes com hirsutismo idiopático (HI), estratificadas de acordo com o índice de massa corporal (IMC &lt;= ou &gt; 25kg/m²). Foram dosados androgênios, SHBG, gonadotrofinas, além de glicose, lipídeos e lipoproteínas, insulina e pró-insulina. Foi também realizado o teste de tolerância oral à glicose (75g) para avaliação da curva de glicose e insulina. Concluímos que as pacientes com PCOS e IMC &gt; 25kg/m² apresentam maior prevalência de obesidade abdominal, de hiperinsulinemia, hipertrigliceridemia e curvas glicêmicas alteradas em relação às pacientes PCOS e IMC &lt;= 25kg/m² e ao grupo controle estudado de pacientes com hirsutismo idiopático

An improved method for the rapid assessment of persisting chylomicron remnant concentrations

Persisting chylomicron remnant concentrations have been linked to premature atherosclerosis. The analysis of persisting chylomicron remnant concentrations by an oral triglyceride tolerance test, however, is time-consuming for the study subjects and requires large resources in the laboratory. Therefore, only small numbers of subjects have been studied in the past. We describe major improvements of the testing procedure in regard of composition of the fatty meal, of patient testing, and measurement of postprandial remnants. Shifting the time of the (ready-to-use) fatty drink from the morning hours to bedtime was well accepted by the study subjects and allowed the analysis of blood samples drawn at the morning with minimal impact on the participants’ time and with minimal interferences by confounding factors ( e.g. smoking, additional food intake, physical activity). Chylomicron remnants were measured by fluorometry of the supernatant after ultracentrifugation. This procedure was sensitive, was specific for chylomicron remnants, and was easy to perform. The biological validity of the improved procedure was evaluated by studying type III hyperlipoproteinemia patients and normolipemic apolipoprotein (Apo) E2 homozygotes. In conclusion, this improved test permits the rapid testing for persisting chylomicron remnants in the clinical routine and in large epidemiological studies.

Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome

Objective: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is associated with gain of function mutations in the leucine-stimulated insulin secretion pathway, we examined whether protein feeding or fasting was responsible for hypoglycemia in affected patients. Study design: Patients with HI/HA (8 children and 6 adults) were studied. All had dominantly expressed mutations of glutamate dehydrogenase and plasma concentrations of ammonium that were 2 to 5 times normal. The responses to a 24-hour fasting test were determined in 7 patients. Responses to a 1.5 gm/kg oral protein tolerance test in 12 patients were compared with responses of 5 control subjects. Results: The median age at onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed beyond age 2 years in 6 patients, and 4 were not given a diagnosis until adulthood. Fasting tests revealed unequivocal evidence of hyperinsulinism in only 1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon that were characteristic of hyperinsulinism. In response to oral protein, all 12 patients with HI/HA showed a fall in blood glucose compared with none of 5 control subjects. Insulin responses to protein loading were similar in the patients with HI/HA and control subjects. Conclusion: The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the HI/HA syndrome. (J Pediatr 2001;138:383-9)

Oral zinc tolerance test in pregnant women

Zinc (Zn) is essential for fetal growth and development, and Zn requirement is increased during pregnancy. The purpose of this study was to determine whether intestinal Zn absorption is increased during pregnancy in order to maintain Zn homeostasis. Oral Zn tolerance test (ZnTT) was performed on 25 healthy pregnant women and 7 healthy non-pregnant female volunteers after the administration of 22.5 mg elemental Zn as sulphate following an overnight fast at a single oral dose. Although the mean baseline plasma Zn level was lower in pregnant women than the controls (P < 0.05), there was no statistically significant difference in Zn absorption as determined by the 2nd- and 3rd-hour plasma Zn levels. The relative dose responses also did not show a significant difference between the pregnant and the control groups. Furthermore, different trimesters and the nutritional status did not have a significant impact on Zn absorption. The results suggest that the lack of a compensatory increase in intestinal Zn absorption in spite of the low Zn status in pregnancy may suggest the intestinal factor as a contributary factor in poor bioavailability. J. Trace Elem. Exp. Med. 14:17–23, 2001. © 2001 Wiley-Liss, Inc.

Oral zinc tolerance test in pregnant women

Zinc (Zn) is essential for fetal growth and development, and Zn requirement is increased during pregnancy. The purpose of this study was to determine whether intestinal Zn absorption is increased during pregnancy in order to maintain Zn homeostasis. Oral Zn tolerance test (ZnTT) was performed on 25 healthy pregnant women and 7 healthy non-pregnant female volunteers after the administration of 22.5 mg elemental Zn as sulphate following an overnight fast at a single oral dose. Although the mean baseline plasma Zn level was lower in pregnant women than the controls (P < 0.05), there was no statistically significant difference in Zn absorption as determined by the 2nd- and 3rd-hour plasma Zn levels. The relative dose responses also did not show a significant difference between the pregnant and the control groups. Furthermore, different trimesters and the nutritional status did not have a significant impact on Zn absorption. The results suggest that the lack of a compensatory increase in intestinal Zn absorption in spite of the low Zn status in pregnancy may suggest the intestinal factor as a contributary factor in poor bioavailability. J. Trace Elem. Exp. Med. 14:17–23, 2001. © 2001 Wiley-Liss, Inc.

Störungen der Glukosetoleranz bei Thalassaemia major

Fragestellung und Hintergrund. Bei Patienten mit Thalassaemia major fuhrt die Hamosiderose haufig zu Endokrinopathien. Wir untersuchten die Entwicklung von Glukosetoleranzstorungen und den Einfluss therapeutischer Masnahmen wie intensivierter Chelattherapie und Diat. Methode und Patienten. 60 Patienten mit Thalassaemia major im Alter von 4–36 Jahren, die regelmasige subkutane Deferoxamininfusionen sowie Bluttransfusionen erhielten, wurden hinsichtlich moglicher Endokrinopathien untersucht. Zur Untersuchung der Insulinsekretion dienten orale und i.-v.-Glukosebelastungen sowie der i.-v.-Glukagontest. Bei Patienten mit gestorter Glukosetoleranz wurde der Einfluss einer intensivierten (i. v.) Deferoxamintherapie und diatetischer Masnahmen auf Blutglukose- und Seruminsulinkonzentrationen untersucht. Ergebnisse. Glukosetoleranzstorungen zahlen ab dem 2. Lebensjahrzehnt zu den 4 haufigsten Hormonerkrankungen bei Patienten mit Thalassaemia major. Storungen der Glukosetoleranz gehen in einem Fruhstadium mit einer Hyperinsulinamie einher, spater entwickelt sich ein Insulinmangeldiabetes durch Erschopfung der β-Zell-Aktivitat. In der Fruhphase der Erkrankung fuhrten bei einigen Patienten eine Intensivierung der Deferoxamintherapie oder alleinige diatetische Behandlung zu einer Verbesserung der Glukosetoleranz. Schlussfolgerungen. Storungen der Glukosetoleranz lassen sich im Fruhstadium durch Diat und Intensivierung der Chelattherapie bessern. Die Manifestation eines Diabetes mellitus kann damit moglicherweise aufgehalten werden. Im fortgeschrittenen Stadium der Glukosetoleranzstorung liegt ein Insulinmangel vor, weshalb eine Insulinsubstitution notwendig wird.

Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice

EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with different polarity and molecular size, i.e. NP-1–NP-6. In an oral glucose tolerance test, NP-1 and 4 inhibited the increase in plasma glucose level. However, in an intraperitoneal glucose tolerance test, such an inhibitory effect was not seen. Thus, the effects of NP-1 and 4 were apparently due to the inhibition of glucose absorption from the intestine. In a sucrose tolerance test, all fractions inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and 4 showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3, 4, 5 and 6 inhibited maltase and sucrase activities and all fractions except for NP-1 showed an inhibitory effect on lipase activity dose-dependently. The inhibition of the increase in plasma glucose level by NP-3, 4, 5 and 6 in the oral sucrose tolerance test and the inhibition of the increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance test were apparently due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively.

Doce cremoso de goiaba adicionado de goma guar e seu efeito hipoglicêmico em indivíduos sadios e diabéticos

Estudos mostram que as fibras solúveis no organismo desempenham melhor controle glicêmico, redução do colesterol sérico, retardam o esvaziamento gástrico, podendo, também, ser metabolizadas no intestino, gerando energia. Empregou-se doce cremoso de goiaba com 1,89% de goma guar, como fonte de fibra solúvel, em indivíduos sadios e diabéticos. Os resultados do Teste Oral de Tolerância à Glicose (TOTG), em 50% dos indivíduos sadios, mostraram que a ingestão simultânea do produto com 4,34g de fibra solúvel ao TOTG promoveu uma significativa redução a nível de 5% (P > 0,05) na glicose plasmática aos 60, 90 e 120 minutos. Houve uma redução significativa (P > 0,05) na glicose plasmática nos indivíduos diabéticos, que receberam o produto com 4,34g de fibra solúvel no TOTG, aos 60 e 120 minutos. O doce cremoso de goiaba por conter 2,89% de fibra solúvel, apresentar baixo valor calórico, ser pronto para o consumo, pode servir como opção para indivíduos sadios e diabéticos.

Intestinal absorption of ursodeoxycholic acid in children and adolescents with inflammatory bowel disease.

Ursodeoxycholic acid absorption in the proximal intestine may be impaired in patients with inflammatory bowel disease. We examined the intestinal absorption of ursodeoxycholic acid by the oral ursodeoxycholic acid tolerance test in 19 children and adolescents with inflammatory bowel disease at various stages, including 8 patients with unoperated Crohn's disease, 3 patients with ileal-resected Crohn's disease, 8 with ulcerative colitis, and 8 healthy control subjects. Ursodeoxycholic acid malabsorption was present in all patients with unoperated Crohn's disease in the first diagnosed active stage, in 3 of 5 patients in a relapsing active stage, and in 2 of 8 patients in remission. Ursodeoxycholic acid absorption was significantly lower in patients in the first diagnosed active stage than in the healthy controls (p < 0.01) or in patients in remission (p < 0.01). There was no significant difference between healthy controls and the patients in a relapsing active stage or in remission. Ursodeoxycholic acid absorption was abnormal during the first postoperative month in patients with ileal-resected Crohn's disease, but normalized over time. Malabsorption of ursodeoxycholic acid was not observed in any patients with ulcerative colitis. These findings suggest that absorption of ursodeoxycholic acid in the proximal intestine is impaired in patients with Crohn's disease and that the oral ursodeoxycholic acid tolerance test is a convenient and useful means of evaluating the absorption of bile acid in the proximal intestine in pediatric patients with ileal or ileocolic Crohn's disease.

Suppression by water extracts of Sophora plants of sucrose-induced hyperglycemia in rats and inhibition of intestinal disaccharidases in vitro.

Partially purified hot-water extracts of the roots of plants of the Sophora family suppressed the increase in blood glucose concentration of rats in the oral sugar tolerance test. The extracts also inhibited rat intestinal sucrase and maltase. The most potent sample was about 15 times more active than catechin, a positive control, in these experiments.