Oral Carbohydrate Tolerance Tests Research Articles

Alpha glucosidase inhibitory activity of hydro-methanolic (2:3) extract of seed of Swietenia mahagoni (L.) Jacq

Objectives: Present study investigated the effect of hydro-methanolic extract of seed of Swietenia mahagoni (HMESM) on a-glucosidase inhibition in normal and streptozotocin-induced diabetic rats. Methods: Oral carbohydrate tolerance tests were performed in 16h fasted normal and diabetic rats loaded with starch or sucrose or glucose at the dose of 3g/kg, 15min after administration of 250 (S1), 500 (S2), 1000 (S3) mg/kg of HMESM, vehicle (control),or pretreatment at the dose of 10 mg/kg of acarbose (Acar). Blood samples were analyzed for glucose levels at 0, 30 th , 60 th , and 120 th min after respective treatments and the peak blood glucose (PBG) levels and area under the curves (AUC) were determined. Results: Results demonstrated that 500mg, 1000mg/kg of HMESM reduced and prolonged the PBG and decreased AUC simultaneously after starch and sucrose loading in normal and diabetic rats. Similarly acarbose also reduce the sucrose and starch induced blood glucose excursion, whereas it had no peak blood glucose suppressive effect after exogenous glucose load in both normal and diabetic rats. On the other hand, phytochemical study of the said extract revealed that it is rich in phenolic compounds (46.25 mg of gallic acid equivalent/g of extract) and flavonoids (231.72mg of quercetin equivalent/g of the extract), which may may responsible for pharmacological activities. Conclusion: The HMESM may have PBG suppressive effect in post-carbohydrate challenged state as evidenced by reduced PBG and AUC. This suggest that HMESM may be used effectively as a safer alternative to control postprandial hyperglycemia especially in pre-diabetic and diabetic patients.

Design, synthesis, and structure–activity relationships of a series of 4-benzyl-5-isopropyl-1H-pyrazol-3-yl β-d-glycopyranosides substituted with novel hydrophilic groups as highly potent inhibitors of sodium glucose co-transporter 1 (SGLT1)

Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of therapeutic options for postprandial hyperglycemia. Previously, we reported potent and selective SGLT1 inhibitors 1 and 2 showing efficacy in oral carbohydrate tolerance tests in diabetic rat models. In a pharmacokinetic (PK) study of 2, excessive systemic exposure to metabolites of 2 was observed, presumably due to the high permeability of its aglycone (2a). To further improve SGLT1 inhibitory activity and reduce aglycone permeability, a series of 4-benzyl-5-isopropyl-1H-pyrazol-3-yl β-d-glycopyranoside derivatives bearing novel hydrophilic substitution groups on the phenyl ring were synthesized and their inhibitory activity toward SGLTs was evaluated. Optimized compound 14c showed an improved profile satisfying both higher activity and lower permeability of its aglycone (22f) compared with initial leads 1 and 2. Moreover, the superior efficacy of 14c in various carbohydrate tolerance tests in diabetic rat models was confirmed compared with acarbose, an α-glucosidase inhibitor (α-GI) widely used in the clinic.

Inhibition of α-Glucosidase by Andrographis paniculata. Ethanol Extract in Rats

In the current study, we investigated the effect of ethanol extract of Andrographis paniculata. (Burm.f.) Nees (Acanthaceae) (AP) on α.-glucosidase (EC 3.2.1.20) inhibition in both normal and streptozotocin-induced diabetic rats. Oral carbohydrate tolerance tests were performed in 18-h fasted rats with starch (3 g/kg), sucrose (4 g/kg), and glucose (2 g/kg) separately, in both normal and diabetic rats, 10 min after administration of 250 (D1), 500 (D2), 1000 (D3) mg/kg ethanol extract of AP, vehicle (control), and acarbose (Acar) 10 mg/kg, respectively. Blood samples were analyzed for blood glucose at 0, 30, 60, and 120 min after respective treatments and the peak blood glucose (PBG) and area under the curve (AUC) determined. Our results demonstrate that 500 mg, 1000 mg/kg ethanol extract of AP reduces and prolongs the PBG concentration, simultaneously decreasing AUC after starch and sucrose loading in normal and diabetic rats. Similarly, acarbose also reduced sucrose and starch induced blood glucose excursions, whereas it had no peak blood glucose suppressive effect after exogenous glucose load in both normal and streptozotocin-induced diabetic rats. The results suggest the possibility that the ethanol extract of AP may have PBG suppressive effect, post–carbohydrate challenge as evidenced by reduced PBG and AUC, which can be used effectively as a safer alternative to control postprandial hyperglycemia (PPH), especially in diabetic patients and borderline patients not properly controlled on diet alone.

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

Apparent Inability of Channel Catfish to Utilize Dietary Mono- and Disaccharides as Energy Sources

Purified diets containing equivalent amounts of glucose, maltose, fructose, sucrose, corn starch and dextrin were fed to fingerling channel catfish (Icatalurus punctatus) to compare the growth responses to these various carbohydrates. The best growth response was achieved with dextrin and the next best with corn starch. Fish grew at the same rate when glucose, maltose or sucrose was the only dietary carbohydrate source. Dietary fructose resulted in the lowest growth rate. Feed efficiency and percent retained energy values followed the same pattern as growth rates. These data suggest that the catfish is apparently unable to utilize dietary mono- and disaccharides as energy sources. Oral carbohydrate tolerance tests using glucose, maltose, fructose, sucrose and dextrin were conducted with larger channel catfish. Oral glucose and maltose resulted in a, persistent hyperglycemia indicative of a diabetic-like status. Fructose appeared to be poorly absorbed from the intestinal tract and did not appear to be converted to glucose. Oral administration of sucrose was followed by a gradual increase in plasma glucose, with no detectable fructose being absorbed until the 6-h period. Oral dextrin resulted in less than a twofold increase in plasma glucose, which remained constant from 2 to 4 h after administration and then declined. These observations are consistent with the hypothesis that certain fishes, including the channel catfish, resemble diabetic animals by having insufficient insulin for maximum carbohydrate utilization.

Influence of somatostatin on carbohydrate absorption in human small intestine

Oral carbohydrate tolerance tests with xylose, galactose and lactose were performed. After an interval of at least 24 h the same tests were repeated following an i.v. bolus and during infusion of somatostatin. Somatostatin does not influence xylose absorption. However, absorption of galactose and lactose is significantly reduced (p less than 0.01/0.008) during somatostatin infusion. On the other hand, serum levels of galactose remain unchanged despite administration of somatostatin, when galactose is given parenterally. The results support the assumption that the absorption process in small intestine is affected by somatostatin. Possible effects of somatostatin on hormones regulating the intestinal absorption and on energy-depending carrier mechanisms are discussed.

Human Intestinal Disaccharidase Activity

DECREASED disaccharidase activity in the small intestine may be primary, or secondary to other small intestinal diseases. 1,2 The diagnosis is established by appropriate oral carbohydrate tolerance tests and assays of the mucosal disaccharidases of the small intestine. The work reported here concerns: (1) the oral lactose tolerance test in normal humans given varying amounts of the test carbohydrate; (2) our normal range of small intestinal disaccharidase and alkaline phosphatase activities; and (3) additional data on the distribution of these enzymes in the duodenum and jejunum. Material and Methods Patients. —Twenty-five individuals were selected for this study on the bases of a negative history of milk or disaccharide intolerance and/or normal disaccharide tolerance tests. The subjects were then classified into two groups. Group 1 consisted of 19 presumably healthy individuals ranging in age from 21 to 46 years; 14 men and 5 women. Seventeen were Caucasian and two were

EFFECT OF SIMPLE AND COMPLEX CARBOHYDRATES ON PLASMA NON-ESTERIFIED FATTY ACIDS, PLASMA-SUGAR, AND PLASMA-INSULIN DURING ORAL CARBOHYDRATE TOLERANCE TESTS

EFFECT OF SIMPLE AND COMPLEX CARBOHYDRATES ON PLASMA NON-ESTERIFIED FATTY ACIDS, PLASMA-SUGAR, AND PLASMA-INSULIN DURING ORAL CARBOHYDRATE TOLERANCE TESTS