Carbohydrate Tolerance Tests Research Articles

Optimized extraction, enrichment, identification and hypoglycemic effects of triterpenoid acids from Hippophae rhamnoides L pomace

The Hippophae rhamnoides L. pomace was generated in the production process for juice, wine of food industry. To expand the application of pomace, the extraction process optimization, enrichment and identification of triterpene acids were performed in this study. The extraction yield was 14.87% under optimal ultrasound-assisted extraction techniques performed via response surface methodology. The extract was subsequently purified to obtain the triterpenoid acid enrichment fraction (TPF) with the content of 75.23% ± 1.45%. 13 triterpenoid acids were identified via UPLC-Triple-TOF MS/MS and further semi-quantified through comparison with triterpenoid acid standards. TPF exhibited a strong inhibitory effect on α-glucosidase with IC50 value of 5.027 ± 0.375 μg/mL, as determined via enzyme inhibition experiment and molecular docking. Additionally, the TPF significantly reduced postprandial glucose levels, as revealed via carbohydrate tolerance tests, as well as ameliorate serum lipid profiles. Therefore, pomace may be a promising resource of functional food components with therapeutic and commercial values.

Comparative evaluation of the antihyperglycemic effects of three extracts of sea mustard (Undaria pinnatifida): In vitro and in vivo studies

Undaria pinnatifida (UP) contains multiple bioactive substances, such as polyphenols, polysaccharides, and amino acids, which are associated with various biological properties. This study aimed to evaluate the antihyperglycemic effects of three extracts obtained from UP. UP was extracted under three different conditions: a low-temperature water extract at 50 °C (UPLW), a high-temperature water extract at 90 °C (UPHW), and a 70 % ethanol extract (UPE). Nontargeted chemical profiling using high-performance liquid chromatography-triple/time-of-flight mass spectrometry (HPLC−Triple TOF−MS/MS) was conducted on the three UP extracts. Subsequently, α-glucosidase inhibitory (AGI) activity, glucose uptake, and the mRNA expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) were evaluated in Caco-2 cell monolayers. Furthermore, an oral carbohydrate tolerance test was performed on C57BL/6 mice. The mice were orally administered UP at 300 mg/kg body weight (B.W.), and the blood glucose level and area under the curve (AUC) were measured. Compared with glucose, UPLW, UPHW and UPE significantly inhibited both glucose uptake and the mRNA expression of SGLT1 and GLUT2 in Caco-2 cell monolayers. After glucose, maltose, and sucrose loading, the blood glucose levels and AUC of the UPLW group were significantly lower than those of the control group. These findings suggest that UPLW has antihyperglycemic effects by regulating glucose uptake through glucose transporters and can be expected to alleviate postprandial hyperglycemia. Therefore, UPLW may have potential as a functional food ingredient for alleviating postprandial hyperglycemia.

A novel polyphenol-rich combination of 5 plant extracts prevents high-fat diet-induced body weight gain by regulating intestinal macronutrient absorption in mice

Global prevalence of obesity and type 2 diabetes are rapidly increasing to pandemic proportions. A novel supplement composed of 5 plant extracts from olive leaf, bilberry, artichoke, chrysanthellum, and black pepper was designed to prevent type 2 diabetes development in people at risk. It was previously shown to improve body weight and glucose control in preclinical rodent models, with these effects being accompanied by increased fecal energy excretion and in vitro inhibition of several digestive enzymes. Thus, we hypothesized that, in mice fed a high-fat diet (HFD), a single dose of this botanical supplementation would decrease the responses to oral fat and carbohydrate tolerance tests, and that chronic supplementation would result in increased fecal triglyceride content. We showed that acute administration in HFD-fed mice (1.452 g/kg body weight) markedly reduced circulating triglycerides following an oral lipid gavage, whereas glycemic responses to various carbohydrate tests were only mildly affected. When incorporated into the food (2.5%) of HFD-fed mice, chronic supplementation prevented body weight gain and improved glucose homeostasis and lipid tolerance. Fecal free fatty acid content, but not triglyceride, was significantly increased in supplemented animals, suggesting reduced lipid absorption in the digestive tract. Congruently, this botanical supplementation downregulated several genes associated with fatty acid transport whose expression was increased by HFD, principally in the jejunum. This study provides novel insights as for the mode of action behind the antiobesity effect of this plant-based supplementation, in HFD-fed mice.

Annona cherimola Miller and Its Flavonoids, an Important Source of Products for the Treatment of Diabetes Mellitus: In Vivo and In Silico Evaluations.

The antihyperglycemic activity of ethanolic extract from Annona cherimola Miller (EEAch) and its products were evaluated using in vivo and in silico assays. An α-glucosidase inhibition was evaluated with oral sucrose tolerance tests (OSTT) and molecular docking studies using acarbose as the control. SGLT1 inhibition was evaluated with an oral glucose tolerance test (OGTT) and molecular docking studies using canagliflozin as the control. Among all products tested, EEAc, the aqueous residual fraction (AcRFr), rutin, and myricetin reduced the hyperglycemia in DM2 mice. During the carbohydrate tolerance tests, all the treatments reduced the postprandial peak such as the control drugs. In the molecular docking studies, rutin showed more affinity in inhibiting α-glucosidase enzymes and myricetin in inhibiting the SGLT1 cotransporter, showing ∆G values of -6.03 and -3.32 kcal/mol-1, respectively, in α-glucosidase enzymes. In the case of the SGLT1 cotransporter, molecular docking showed ∆G values of 22.82 and -7.89 in rutin and myricetin, respectively. This research sorts in vivo and in silico pharmacological studies regarding the use of A. cherimola leaves as a source for the development of new potential antidiabetic agents for T2D control, such as flavonoids rutin and myricetin.

In vitro and in vivo postprandial hypoglycemic effects and comprehensive metabolite profiling of Dangjo chili pepper (Capsicum annuum L. cv. Dangjo)

The Dangjo chili pepper (DJ) has been reported to contain various compounds with α-glucosidase inhibitory activity. However, the hypoglycemic effect of DJ and the active ingredients responsible have not been fully investigated. Herein, the current study aimed to examine DJ as a novel α-glucosidase inhibitor for the prevention of hyperglycemia. The identification of metabolites and the assessment of α-glucosidase inhibitory activity was conducted in three chili pepper species. Glucose uptake inhibition by DJ ethanol extract (DJE) was evaluated in Caco-2 cells. Furthermore, an oral carbohydrate tolerance test was performed in C57BL/6 mice. A total of 18 metabolites were identified in Dangjo, Green, and Cucumber chili peppers. Among these, quercitrin was one the most abundant flavonoid in DJ. The DJ showed the highest inhibition of α-glucosidase activity against both maltose and sucrose compared to other peppers. In addition, isoorientin, quercitrin, and DJE had similar inhibitory activities for both substrates. Glucose uptake was significantly inhibited in the DJE group compared to the control group. The mice were orally administered freeze-dried DJ at 150 and 300 mg/kg body weight (B.W.), and blood glucose levels were measured. Under glucose loading, both groups had significantly reduced blood glucose concentration compared to the control group (p = 0.001). Under maltose loading, the blood glucose concentration was decreased in the 150 mg/kg B.W. group compared to the control group (p = 0.025). These results indicate that Dangjo chili pepper has the potential to function as a postprandial hypoglycemic agent by inhibiting the α-glucosidase activity.

Eight weeks of lentil consumption attenuates insulin resistance progression without increased gastrointestinal symptom severity: A randomized clinical trial

Lentils lower acute glycemic responses and promote satiety, benefits that may aid in chronic disease prevention. However, perceived gastrointestinal (GI) effects may deter inclusion of dietary pulses in the diet. We hypothesized that 8 weeks of lentil-based vs meat-based meals would improve glycemic control and improve satiety in metabolically at-risk, nondiabetic adults. Because GI symptoms are rarely reported, we also explored the temporal effects of symptom severity. Adults with an increased waist circumference (male > 40 inches, female > 35 inches) participated in an 8-week dietary intervention that included 5 prepared midday meals each week that were isocaloric but varied in cooked green lentil dosage: 0 g (CON), 300 g (MOD), or 600 g (HI). Assessments included glucose and insulin integrated area under the curve measured during a 75-g carbohydrate tolerance test, hepatic Homeostatic Model of Insulin Resistance (HOMA-IR), and peripheral insulin resistance. On 1 randomized day each week, satiety was assessed at 4:00 pm and GI symptoms at 8:00 pm. A linear model assessed changes in glycemic and GI measures by meal group. Thirty adults (mean ± SD; age, 41.6 ± 11.7 years, body mass index, 35.1 ± 6.3) completed the intervention. HOMA-IR increased in CON (+1.2 units) and decreased in a dose-dependent manner in MOD (–0.9 units, P = .03) and HI (–1.5 units, P < .01) relative to CON. Most participants (87.4%) reported no to mild GI symptoms. Of these, flatulence was mild on average with bloating, abdominal discomfort, and cramping severity 0.3, 0.5, and 0.5 units lower (P < .001). We observed a dose-dependent reduction on rising hepatic insulin resistance and low GI symptom severity with long-term lentil consumption in metabolically at-risk adults.

Antihyperglycemic Effects of Salvia polystachya Cav. and Its Terpenoids: α-Glucosidase and SGLT1 Inhibitors.

The antihyperglycemic activity of ethanolic extract from Salvia polystachya (EESpS) and its products was evaluated using in vivo, ex vivo and in silico assays; additionally, an acute toxicity assay was evaluated. EESpS was classified as a nontoxic class 5 drug. EESpS, ethyl acetate fraction (EtOAcFr), secondary-6-fraction (SeFr6), ursolic acid (UA), and oleanolic acid (OA) reduced the hyperglycemia in DM2 mice. α-glucosidase inhibition was evaluated with oral sucrose and starch tolerance tests (OSuTT and OStTT), an intestinal sucrose hydrolysis (ISH) assay and molecular docking studies using acarbose as control. SGLT1 inhibition was evaluated with oral glucose and galactose tolerance tests (OGTT and OGaTT), an intestinal glucose absorption (IGA) assay and molecular docking studies using canagliflozin as the control. During the carbohydrate tolerance tests, all the treatments reduced the postprandial peak, similar to the control drugs. During the ISH, IC50 values of 739.9 and 726.3 µM for UA and OA, respectively, were calculated. During the IGA, IC50 values of 966.6 and 849.3 for UA, OA respectively, were calculated. Finally, during the molecular docking studies, UA and OA showed ∆G values of −6.41 and −5.48 kcal/mol−1, respectively, on α-glucosidase enzymes. During SGLT1, UA and OA showed ∆G values of −10.55 and −9.65, respectively.

The new angiotensin II receptor blocker Edarbi® as part of the pathogenetic treatment of arterial hypertension in patients with metabolic disorders

Relevance. Recently, the proportion of angiotensin receptor blockers has significantly increased among prescribed antihypertensive drugs. High organoprotective properties, additional metabolic effects and tolerability comparable to placebo make them the drugs of choice, especially in patients with stage 1 and stage 2 hypertension having low adherence to antihypertensive therapy, but already burdened by additional metabolic risk factors. Purpose of the study - study of the antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil (Edarbi®), its effect on cardiometabolic risk factors and damage of target organs in patients with stage 2 hypertension. Materials and methods. The study included 32 patients (mean age 47.32±8.4 years), 19 men and 13 women with stage 2 hypertension. All patients were evaluated for clinical blood pressure (BP), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, creatinine, glucose level in a carbohydrate tolerance test, 24-hour blood pressure monitoring, central aortic systolic pressure, сarotid-femoral pulse wave velocity and intima-media thickness was determined initially and after 6 months of therapy. Results. During taking Edarbi® 82% of patients with stage 1 and stage 2 hypertension and metabolic syndrome reached the target level of BP, which was accompanied by a significant improvement in diastolic function of the left ventricle in 56% of patients. Already in the first 6 months the treatment reduced arterial stiffness and improved metabolic control

Clinical significance of autoantibody assay in children with lupus erythematosus accompanied with diabetes mellitus

Objective To investigate the correlation between juvenile lupus erythematosus and type 1 diabetes mellitus and pancreatic injuries. Methods In this prospective study, 74 children with system lupus erythematosus (SLE), 5 cases with neonatal lupus erythematosus (NLE) admitted in Department of Rheumatism and Immunology of Children's Hospital Affiliated to Capital Institute of Pediatrics from March 2007 to March 2015 and 30 healthy children as normal controls were enrolled. Islet cell antibodies (ICA), insulin autoantibodies (IAA) and glutamic acid decarboxylase antibodies (GADA) of each subject were detected by enzyme-linked immunosorbent assay (ELISA), random blood glucose and fasting blood glucose by hexokinase method as well as glycosylated hemoglobin by high performance liquid chromatography. Detailed monitoring of the symptoms, signs and autoantibodies were recorded. Carbohydrate tolerance test arranged for some patients and three kinds of antibodies above were detected during the recovery period. χ2 test was used to test the relativity between activities of disease and autoantibodies including ICA, IAA and GADA in the children with lupus erythematosus. Results Among 74 children with systemic lupus erythematosus, 2 cases were found the fasting blood glucose 6.5%. All the 6 cases were transitional hyperglycemia with random blood sugar>11.1 mmol/L. The glucose tolerance test of the 6 patients above were normal, which could exclude the diagnose of diabetes mellitus. One of 74 patients was positive ICA. For IAA, 24 patients were positive and 21 cases with positive GADA were detected. In all 74 patients, there were 36 cases with one positive antibody while 9 cases with positive IAA and GADA simultaneously. In 5 children with NLE, 2 cases were found with positive IAA and GADA simultaneously, 1 case with positive IAA only and 2 cases with all 3 antibodies negative. There was a statistically significant difference between SLE, NLE and the normal group in ICA, IAA, GADA positive rate (P<0.001). The positive rates of ICA, IAA and GADA were 1.35%(1/74), 32.43%(24/74) and 28.38%(21/74)in SLE group; the positive rates of ICA, IAA, GADA were 0, 3/5 and 2/5 in NLE group; the positive rates of ICA, IAA and GADA were 0, 0 and 3.33%(1/30)in the control group (ICA: χ2=12.649, P<0.001; GADA: χ2=8.028, P=0.005). Of 8 cases with positive antibodies who received tests of their positive antibodies during the periods of recovery, 6 cases were detected with positive IAA, of whom 4 turned negative. In 5 cases with positive GADA, 4 turned negative. Only 1 in 30 healthy children of the normal control was found with GADA positive. Conclusions Relatively high rates of positive diabetes mellitus related antibodies were detected in current study. Diabetes mellitus related antibodies could be detected in children with SLE and even in neonates with lupus erythematosus. Blood glucose should be tested and monitored to detect the possibility of concomitant type 1 diabetes mellitus in children with SLE.(Chin J Lab Med, 2016, 39: 829-832) Key words: Lupus erythematosus, systemic; Insuli antibodies; Autoantibodies; Glutamate decarboxylase; Blood glucose

Identification of informative bands in the short-wavelength NIR region for non-invasive blood glucose measurement.

The "glucose-linked wavelength" in the short-wavelength near-infrared (NIR) region, in which the light intensity reflected from the hand palm exhibits a good correlation to the blood glucose value, was investigated. We performed 391 2-h carbohydrate tolerance tests (CTTs) using 34 participants and a glucose-linked wavelength was successfully observed in almost every CTT; however, this wavelength varied between CTTs even for the same person. The large resulting data set revealed the distribution of the informative wavelength. The blood glucose values were efficiently estimated by a simple linear regression with clinically acceptable accuracies. The result suggested the potential for constructing a personalized low-invasive blood glucose sensor using short-wavelength NIR spectroscopy.

Effect of Costus afer on Carbohydrates Tolerance Tests and Glucose Uptake

Diabetes is commonly characterized by hyperglycemia related to different mechanisms. Many plants have been reported to possess antidiabetic actions in lowering blood sugar concentration and one of such is Costus afer. The present study hypothesis is that methanolic extract of C. afer (leaf, stem, and rhizome) control hyperglycemia by inhibiting glucose uptake. Glucose uptake inhibition was carried out by incubating glucose with plant extract of varying dosages in yeast cells. The carbohydrate tolerance tests characterized by starch and maltose tolerance tests were carried out by loading two sets of experimental animals with respective carbohydrate and varying dosages of C. afer extract. In both studies metformin was used as the reference drug. C. afer extracts significantly inhibited the uptake of glucose by yeast cells. The percentage inhibition was below 50 % for all extracts with a dose dependent effect. The methanolic leaf extract of C. afer had the highest effect followed by stem and rhizome. The inhibition potential of C. afer leaf extract was comparable to that of metformin the reference drug. Similar results were obtained in the carbohydrate tolerance test. Groups of rats treated with plant extracts had lower blood glucose level compared to the groups that treated with carbohydrates only. Metformin was significantly better than plant extracts in the lowering of blood sugar. The result obtained is a proof of concept that C. afer possess antidiabetic properties though more need to be done to effectively confirm its use as an antidiabetic agent.

PWE-062 Fructose Intolerance in Pelvic Radiation Disease; Is It More Common than We Realised?

Introduction Guidelines have recently been published regarding the management of Pelvic Radiation Disease (PRD) and late effects of cancer care. 1 The guidelines have been shown in peer reviewed studies to be effective in the management of PRD. 2 The guidelines include a number of investigations for certain symptoms and include carbohydrate tolerance tests for substrates such as fructose. That said there are currently no published case series or studies evaluating the prevalence and diagnostic yield of fructose breath testing in PRD. We have recently set up a dedicated late effects of cancer care and pelvic radiation disease clinic in Cardiff and audited the results of our fructose tolerance breath tests. Patients with diarrhoea, bloating or abdominal pain were investigated with fructose breath testing as per these guidelines. Methods We audited the results for all fructose breath tests in 2014 in patients with suspected PRD via a database search and correlation with clinical notes. Total of 82 patients were identified as having a fructose breath tests in the 1 year period) 20 of which were being investigated for suspected PRD. (10 Male, 10 female, median age 65.5) Results 45% of fructose breath tests in patients with suspected PRD were positive (n = 9) All of these patients were referred with either diarrhoea, bloating or abdominal pain. Of these patients with positive tests, 44% were found to have a dual pathology (n = 4) with other diagnoses including small intestinal bacterial overgrowth, lactose intolerance and bile acid diarrhoea. Conclusion Fructose intolerance is common in patients with diarrhoea, bloating and abdominal pain in PRD. The diagnostic yield of testing is high and should be considered as a differential diagnosis in these patients. It is important to recognise that dual pathology frequently occurs and that an algorithmic approach is useful in these patients. References 1 Andreyev HJN, Muls AC, Norton C, Ralph C, Watson L, Shaw C, et al . Guidance: The practical management of the gastrointestinal symptoms of pelvic radiation disease. Frontline Gastroenterology [Internet]. BMJ Publishing Group Ltd; 2014 Jun 17;flgastro–2014–100468. Available from: http://fg.bmj.com/content/early/2014/06/17/flgastro-2014-100468.abstract 2 Andreyev HJN, Benton BE, Lalji A, Norton PC, Kabir M, GaugeGage PH, et al . ArticlesAlgorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial. Lancet. Elsevier Ltd; 2013 Sep 20;1–9. Disclosure of Interest None Declared

Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats.

Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.

Carbohydrate and lipid metabolism in the patients differing in the degree of gestational body weight gain

Aim. To elucidate the character of the relationship between gestational body weight gain (GBWG) and carbohydrate/lipid metabolism during pregnancy. Material and methods. This prospective cohort study enrolled 85 women with full-term sigleton pregnancy in the absence of signs of diabetes mellitus or severe somatic pathology including 15 ones with subnormal GBWG, 35 with excessive GBWG, and 36 with recommended GBWG. Detection of gestational body weight gain, carbohydrate tolerance test, measurement of baseline and stimulated insulin secreation, lipidograms obtained in the first, second, and third trimesters. Results. The biochemical profile in the patients with pathological GBWG has the following peculiarities in comparison with that of the women with recommended GBWG during pregnancy. The women with excessive GBWG in the second and third trimesters are characterized by enhanced levels of baseline and stimulated insulin secretion, high HOMO-IR index and LDLP concentration (p&lt;0.05). The women with subnormal GBWG in the first trimester have a higher fasting blood glucose level whereas in the third trimester both fasting glycemia and insulin concentration in response to standard carbohydrate loading decrease to below the respective normal values (p&lt;0.05). The biochemical and hormonal characteristics of carbohydrate and lipid metabolism undergo secondary changes following body mass variations. Conclusion. The results of this study show that changes in sensitivity to insulin are in all probability the consequence of pathological enhancement of body mass rather than its cause.

Inhibitory effects of polyphenols from water chestnut (Trapa japonica) husk on glycolytic enzymes and postprandial blood glucose elevation in mice

Water chestnut is an annual aquatic plant that grows in Asia and Europe. Although water chestnut has been used as food and herbal medicine, its physiological functions and active ingredients are unknown. Here, we extracted polyphenols from the husk of the Japanese water chestnut (Trapa japonica) and assessed their effects on blood glucose levels. Three hydrolysable polyphenolics (WCPs), eugeniin, 1,2,3,6-tetra-O-galloyl-β-d-glucopyranose, and trapain, were predominant with dry-weight contents of 2.3±0.0, 2.7±0.1, and 1.2±0.1g/100g, respectively. These WCPs exhibited inhibitory activity against α-amylase and α-glucosidase. Whereas (−)-epigallocatechin gallate does not inhibit α-amylase, WCPs exhibited high inhibitory activity (>80% at 0.15mg/mL). In mice, administration of WCPs (40mg/kg) significantly reduced blood glucose and serum insulin levels as assessed by the carbohydrate tolerance test.

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.

Structure–activity relationship studies of 4-benzyl-1H-pyrazol-3-yl β-d-glucopyranoside derivatives as potent and selective sodium glucose co-transporter 1 (SGLT1) inhibitors with therapeutic activity on postprandial hyperglycemia

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 treatments for postprandial hyperglycemia. A series of 4-benzyl-1H-pyrazol-3-yl β-d-glucopyranoside derivatives have been synthesized, and its inhibitory activity toward SGLTs has been evaluated. By altering the substitution groups at the 5-position of the pyrazole ring, and every position of the phenyl ring, we studied the structure–activity relationship (SAR) profiles and identified a series of potent and selective SGLT1 inhibitors. Representative derivatives showed a dose-dependent suppressing effect on the escalation of blood glucose levels in oral mixed carbohydrate tolerance tests (OCTT) in streptozotocin–nicotinamide-induced diabetic rats (NA-STZ rats).

Reduction in post-prandial hyperglycemic excursion through α-glucosidase inhibition by β-acetamido carbonyl compounds

A series of β-acetamido carbonyl compounds ( S 1– S 7) were prepared using Dakin-West reaction from different substituted aldehyde and acetophenone in the presence of lanthanum triflate as a solid catalyst. All the compounds were tested for their α-glucosidase inhibitory potential against rat intestinal α-glucosidase. The most potent rat intestinal α-glucosidase inhibitors S 5 and S 7 were tested for their antihyperglycemic activity following carbohydrate tolerance test. Both the compounds displayed antihyperglycemic activity equivalent to the standard drug acarbose.

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.