Lower Postprandial Glucose Research Articles

Benefit of supplementary fat plus protein counting as compared with conventional carbohydrate counting for insulin bolus calculation in children with pump therapy

To investigate carbohydrate (CARB) and supplementary fat/protein (CFP) counting using normal and dual-wave bolus in pump therapy of children and young people with type 1 diabetes (T1D). A randomized clinical trial was conducted in 42 patients (age 6-21 yr) with T1D for at least 1 yr (5.2 ± 3.1 yr, mean ± SD) and pump therapy for at least 3 months (3.3 ± 1.8 yr). Standardized test meals (pizza-salami; 50% carbohydrate, 34% fat, 16% protein; corresponding to 33% of age-adjusted daily energy requirement) were given at lunch time on four different days with normal and dual-wave bolus using CARB and CFP counting in a randomized sequence. Sensor-augmented pumps were used for continuous glucose monitoring of 6-h postprandial glucose profiles. Intra-individual comparisons of glucose parameters [area under the curve (AUC) mg/dL × 6 h; average glucose, AV mg/dL] were performed. Using CFP counting, 6-h postprandial glucose AUC (805 ± 261) and AV (137.8 ± 46.2) were significantly lower than AUC (926 ± 285) and AV (160.5 ± 51.9) by CARB counting (p < 0.001, each). CFP counting led to significantly lower postprandial glucose parameters independently from the kind of bolus (normal bolus: ΔAUC 169, p < 0.001; ΔAV 30.6, p < 0.001/dual-wave bolus: ΔAUC 73, p = 0.045, ΔAV 14.8, p = 0.033). Postprandial hypoglycemia episodes (<70 mg/dL) occurred more frequently in CFP than in CARB counting (35.7% vs. 9.5%, p < 0.001). No severe hypoglycemia was reported. In patients with long-term T1D, meal-related insulin dosing based on carbohydrate plus fat/protein counting reduces the postprandial glucose levels (ClinicalTrials.gov NCT01400659).

A Chitinase-Like Protein with α-Amylase Inhibitory Activity from Kluai Hom Thong Banana Fruit: Musa (AAA group)

Diabetes is a syndrome of disordered metabolism resulting in abnormally high blood sugar levels (hyperglycemia). The one possibility of lowering postprandial glucose levels is by the inhibition of α-amylase activity. In this study, aqueous extracts from local Thai fruits were tested for their inhibitory effect on α-amylase. The results showed that the fruits of Kluai Hom Thong; Musa (AAA group) showed significant reduction in α-amylase activity. An α-amylase inhibitor was purified by using a combination of ammonium sulfate precipitation, ion exchange chromatography with DEAE cellulose, and gel filtration chromatography with Superdex 75, respectively. The enriched preparation had a specific activity of 355.7 AI U/mg proteins for a yield of 18.5% total protein. The molecular weight of this α-amylase inhibitor was estimated by SDS-15% (w/v) PAGE to be about ∼20 kDa. Periodic staining and phenol-sulfuric assay showed that the α-amylase inhibitor was a glycoprotein and contained 10.74 ± 0.35% (by weight) carbohydrate moiety. The pH stability of this α-amylase inhibitor was between pH 4 and 7, and it is stable up to 40°C but is totally inactivated after exposure to 40°C for 120 min. The α-amylase inhibitory activity was stimulated by Ca2+ and Mn2 at less than 25 mM but not by Mg2+, Fe3+, Hg2+, Co2+, and EDTA. Determination of the kinetics of the inhibition of α-amylase by standard enzymatic methods indicated the Ki of this protein was 0.89 mg protein/mL. The amino acid sequence of an internal fragment of this purified α-amylase inhibitor had a similarity to the sequence from the plant lectin/endochitnase1 family.

GLP‐1 based therapies: differential effects on fasting and postprandial glucose

Glucagon-like peptide-1 (GLP-1), a gut-derived hormone secreted in response to nutrients, has several glucose and weight regulating actions including enhancement of glucose-stimulated insulin secretion, suppression of glucagon secretion, slowing of gastric emptying and reduction in food intake. Because of these multiple effects, the GLP-1 receptor system has become an attractive target for type 2 diabetes therapies. However, GLP-1 has significant limitations as a therapeutic due to its rapid degradation (plasma half-life of 1-2 min) by dipeptidyl peptidase-4 (DPP-4). Two main classes of GLP-1-mediated therapies are now in use: DPP-4 inhibitors that reduce the degradation of GLP-1 and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists. The GLP-1R agonists can be further divided into short- and long-acting formulations which have differential effects on their mechanisms of action, ultimately resulting in differential effects on their fasting and postprandial glucose lowering potential. This review summarizes the similarities and differences among DPP-4 inhibitors, short-acting GLP-1R agonists and long-acting GLP-1R agonists. We propose that these different GLP-1-mediated therapies are all necessary tools for the treatment of type 2 diabetes and that the choice of which one to use should depend on the specific needs of the patient. This is analogous to the current use of modern insulins, as short-, intermediate- and long-acting versions are all used to optimize the 24-h plasma glucose profile as needed. Given that GLP-1-mediated therapies have advantages over insulins in terms of hypoglycaemic risk and weight gain, optimized use of these compounds could represent a significant paradigm shift for the treatment of type 2 diabetes.

Discovery of (S)-6-(3-Cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic Acid as a Hepatoselective Glucokinase Activator Clinical Candidate for Treating Type 2 Diabetes Mellitus

Glucokinase is a key regulator of glucose homeostasis, and small molecule allosteric activators of this enzyme represent a promising opportunity for the treatment of type 2 diabetes. Systemically acting glucokinase activators (liver and pancreas) have been reported to be efficacious but in many cases present hypoglycaemia risk due to activation of the enzyme at low glucose levels in the pancreas, leading to inappropriately excessive insulin secretion. It was therefore postulated that a liver selective activator may offer effective glycemic control with reduced hypoglycemia risk. Herein, we report structure-activity studies on a carboxylic acid containing series of glucokinase activators with preferential activity in hepatocytes versus pancreatic β-cells. These activators were designed to have low passive permeability thereby minimizing distribution into extrahepatic tissues; concurrently, they were also optimized as substrates for active liver uptake via members of the organic anion transporting polypeptide (OATP) family. These studies lead to the identification of 19 as a potent glucokinase activator with a greater than 50-fold liver-to-pancreas ratio of tissue distribution in rodent and non-rodent species. In preclinical diabetic animals, 19 was found to robustly lower fasting and postprandial glucose with no hypoglycemia, leading to its selection as a clinical development candidate for treating type 2 diabetes.

A diet lower in digestible carbohydrate results in lower postprandial glucose concentrations compared with a traditional canine diabetes diet and an adult maintenance diet in healthy dogs

The aim of this study was to compare the effects of three diets with varying macronutrient and fibre contents on postprandial plasma glucose, triglyceride, free fatty acid, and insulin concentrations over a 12h period in 12 healthy neutered lean dogs. Each diet was fed to each dog for 3weeks in a three-period cross-over study. Plasma analyte concentrations were measured prior to and after a meal at the end of the third week of each period. Postprandial glucose concentrations for the moderate carbohydrate and fibre diet were 0.4–0.7mmol/L (8–12mg/dL) lower than for both higher carbohydrate diets (p⩽0.02). Postprandial glucose, insulin, and triglyceride concentrations in some dogs did not return to baseline by 12h after feeding of each of the three diets. These results indicate that the moderate carbohydrate and fibre diet warrants evaluation in diabetic dogs. Variables should be measured over at least 12h after feeding to fully evaluate postprandial dietary effects on these analytes.

Do we really know why diabetes remits after gastric bypass surgery?

Roux-en-Y gastric bypass surgery (GBP) results in 30-40% sustained weight loss and improved type 2 diabetes in up to 80% of patients. The relative contribution of the gut neuroendocrine changes after GBP versus the weight loss has not been fully elucidated. There are clear differences between weight loss by GBP and by dietary intervention or gastric banding. One of them is the enhanced post-prandial release of incretin hormones and the recovery of the incretin effect on insulin secretion after GBP, not seen after diet-induced weight loss. The favorable changes in incretin hormones after GBP result in recovery of the early phase insulin secretion and lower post-prandial glucose levels during oral glucose administration. The enhanced incretin response may be related to the neuroglycopenia post-GBP. In parallel with changes of glucose metabolism, a larger decrease of circulating branched-chain amino acids in relation to improved insulin sensitivity and insulin secretion is observed after GBP compared to diet. The mechanisms of the rapid and longterm endocrine and metabolic changes after GBP are not fully elucidated. Changes in rate of eating, gastric emptying, nutrient absorption and sensing, bile acid metabolism, and microbiota may all be important. Understanding the mechanisms by which incretin release is exaggerated post-prandially after GBP may help develop new less invasive treatment options for obesity and diabetes. Equally important would be to identify biological predictors of success or failure and to understand the mechanisms of weight regain and/or diabetes relapse.

Lower postprandial glucose responses at baseline and after 4 weeks use of a diabetes-specific formula in diabetes type 2 patients

AimsTo determine whether lower postprandial glucose (PPG) levels after intake of a diabetes-specific formula (DSF) compared with a standard formula were maintained after 4 weeks use. MethodsRandomized, controlled, double-blind, parallel-group study. Forty-four type 2 diabetes patients on oral anti-diabetes medication consumed 2×200mL/day of a DSF (Diasip®) or an isocaloric standard, fiber-containing formula for 4 weeks. PPG responses were assessed at baseline and after 4 weeks by iAUC and (delta) peak glucose concentrations. ResultsPPG response was significantly lower in the DSF group after first intake and remained significantly lower after 4 weeks use. Postprandial insulin, fasting glucose, insulin resistance, fructosamine and lipid levels did not differ between groups after 4 weeks. Within the standard group, fasting glucose and HOMAIR significantly increased over the intervention period. Changes in body weight between groups were significantly different, with an increase in the standard group. Both products were equally well tolerated. ConclusionsSuperior PPG control by DSF was maintained after 4 weeks use, showing that this formula has added value with respect to PPG control for type 2 diabetes patients compared to a standard, fiber-containing formula. The observed effects on body weight, fasting glucose and HOMAIR may further support the use of a DSF.

Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats

Type 2 diabetes and chronic heavy alcohol consumption each have been known to be associated with the impairment of hippocampus-dependent cognitive functions. Although both conditions often coexist clinically and there is accumulated evidence of a relationship between the two, the combined effect on hippocampal long-term potentiation (LTP) has not yet been investigated. We compared the effect of type 2 diabetes itself with that of type 2 diabetes with chronic heavy alcohol consumption on the hippocampal LTP using Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, which resembles the characteristics of human type 2 diabetes. Ten of 16-week-old male OLETF rats were randomized into two treatment groups according to weight: the OLETF–Alcohol (O–A, n = 5) and the OLETF–Control (O–C, n = 5). The rats in the O–A group were fed Lieber-DeCarli Regular EtOH over a 10-week period and the amount of alcohol consumption was 8.42 ± 2.52 g/kg/day. To ensure the effect of poor glycemic control on LTP, intraperitoneal glucose tolerance test was performed after a 10-week treatment. The hippocampal LTP was measured by extracellular field excitatory post-synaptic potentials at Shaffer collateral (SC) synapses in the CA1 region. Although the O–A group showed significantly lower fasting and postprandial glucose ( P < 0.01 and P = 0.02, respectively), the hippocampal LTP was more significantly attenuated in the O–A group than the O–C group ( P = 0.032). The results of this study suggested that chronic heavy alcohol consumption could potentiate the impairment of hippocampal LTP in individuals with impaired glucose tolerance or early type 2 diabetes, even though it did not aggravate, but did improve glycemic control. Clinical attention to chronic heavy drinking will be required in preventing cognitive impairment in individuals with type 2 diabetes.

Aerobic Exercise Rapidly Improves Postprandial Glycemia in Free-living Individuals with Type 2 Diabetes

Postprandial glucose excursions (PPG; difference between pre- and post-meal blood glucose concentrations) better predict adverse cardiovascular outcomes than HbA1c in those with and without type 2 diabetes. Exercise training effectively lowers HbA1c and improves insulin sensitivity in persons with type 2 diabetes; however, HbA1c provides only an index of average blood glucose over 2-3 months and does not adequately capture PPG. PURPOSE: To determine the impact of a week-long aerobic exercise intervention on PPG in free-living individuals with type 2 diabetes. METHODS: Using continuous glucose monitors, we quantified mean PPG in sedentary, obese volunteers with non-insulin dependent type 2 diabetes during three days of habitual activity and during the final three days of a seven-day exercise program (60 min·d-1 moderate intensity walking and cycling). Oral glucose tolerance tests (OGTT) were performed on the morning immediately following each monitoring period. Dietary intake was standardized across monitoring periods, and additional snacks were provided to compensate for the energy cost of exercise. RESULTS: Increasing physical activity (5,801 ± 770 to 10,894 ± 791 steps·d-1) for seven days in obese, sedentary patients with type 2 diabetes (N=13, Age 53 ± 2 y, BMI 34.1 ± 1.3 kg·m-2, HbA1c 6.6 ± 0.2%) attenuated PPG up to 40% (1.3 ± 0.2, 2.9 ± 0.3, 3.1 ± 0.3, and 2.4 ± 0.3 mmol·l-1 pre-exercise to 0.8 ± 0.1, 2.1 ± 0.2, 2.0 ± 0.2, and 1.3 ± 0.2 mmol·l-1 post-exercise at 30, 60, 90, and 120 min post-meal, respectively, p < 0.05). Fasting blood glucose (7.0 ± 0.4 to 6.8 ± 0.4 mmol·l-1) and insulin (66.8 ± 8.5 to 65.9 ± 7.1 pmol·l-1) did not change, nor did glucose (1530 ± 93 to 1506 ±77 glucose AUC0-120) and insulin (34,986 ± 5,502 to 29,304 ± 4,188 insulin AUC0-120) responses to the OGTT; however, the Matsuda insulin sensitivity index increased from 3.0 ± 0.3 to 3.6 ± 0.6 (p < 0.05). Body weight and composition were unchanged. CONCLUSIONS: Acute alterations in physical activity significantly lower postprandial glucose excursions, an independent predictor of adverse cardiovascular outcomes, in free living persons with type 2 diabetes. Further, these changes occurred independent of changes in adiposity and were not captured by OGTT. Supported by MU ICATS, NIH T32 AR-048523, Diabetes Action Research and Education Foundation, and VHA CDA.

In vitro Postprandial Glucose Lowering Effects of Dietary Fibers Isolated from Tamarindus indica and Cassia fistula Seeds

In vitro Postprandial Glucose Lowering Effects of Dietary Fibers Isolated from Tamarindus indica and Cassia fistula Seeds

Dietary supplementation with hydroxypropyl-distarch phosphate from waxy maize starch increases resting energy expenditure by lowering the postprandial glucose-dependent insulinotropic polypeptide response in human subjects

The aim of the present study was to investigate the effects of hydroxypropyl-distarch phosphate (HDP) supplementation on postprandial energy metabolism and glucose-dependent insulinotropic polypeptide (GIP) in human subjects. A total of ten healthy male subjects, with a mean BMI of 23·6 (SEM 1·3) kg/m(2), age 35·2 (SEM 1·9) years and body weight 71·1 (SEM 4·0) kg, participated in a randomised, cross-over, intervention study with two different test meals (1673·6 kJ) containing either waxy maize starch or HDP from waxy maize starch (degree of substitution 0·154, P content 0·004 %). Resting energy expenditure (REE) and blood concentrations of various biomarkers were measured at fasting and up to 180 min postprandially. Indirect calorimetry showed that the HDP meal caused higher REE (P < 0·05) and fat utilisation (P < 0·001) than the waxy maize starch meal. The HDP meal led to significantly lower postprandial glucose (P < 0·05), insulin (P < 0·05) and GIP (P < 0·05) responses than the waxy maize starch meal. Both postprandial REE (R - 0·576, P < 0·01) and fat utilisation (R - 0·514, P < 0·05) were negatively correlated with the postprandial GIP response, but not with the glucose and insulin responses. In conclusion, dietary supplementation with HDP lowers postprandial GIP and increases postprandial REE and fat utilisation in healthy humans. An HDP-rich diet may therefore have beneficial implications in weight management. Further studies are required to confirm the efficacy in overweight or obese subjects, and to determine the precise mechanisms.

A Comparison of Twice-Daily Biphasic Insulin Aspart 70/30 and Once-Daily Insulin Glargine in Persons With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Therapy: A Randomized, Open-Label Study

To compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs. In a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control on basal insulin (glargine or neutral protamine Hagedorn) + oral antidiabetic drugs were randomly assigned to twice-daily BIAsp 30 + metformin or once-daily glargine + metformin + secretagogues (secretagogues were discontinued in the BIAsp 30 arm). One hundred thirty-seven patients were randomly assigned to the BIAsp 30 group and 143 patients were randomly assigned to the glargine group. Of 280 patients randomized, 229 (81.8%) completed the study. End-of-trial hemoglobin A1c reductions were -1.3% (BIAsp 30) vs -1.2% (glargine) (treatment difference: 95% confidence interval, -0.06 [-0.32 to 0.20]; P = .657). Of patients taking BIAsp 30, 27.3% reached a hemoglobin A1c level <7.0% compared with 22.0% of patients taking glargine (treatment difference: P = .388). Glucose increment averaged over 3 meals was lower in the BIAsp 30 arm (treatment difference: -17.8 mg/dL, P = .001). Fasting plasma glucose reductions from baseline were -13.8 mg/dL (BIAsp 30) vs -42.5 mg/dL (glargine) (P = .0002). Final minor hypoglycemia rate, insulin dose, and weight change were higher in the BIAsp 30 arm (6.5 vs 3.4 events/patient per year, P<.05; 1.19 vs 0.63 U/kg; and 3.1 vs 1.4 kg, P = .0004, respectively). Despite not receiving secretagogues, patients taking BIAsp 30 + metformin achieved similar hemoglobin A1c levels and lower postprandial plasma glucose compared with those receiving glargine + metformin + secretagogues. The large improvement in the glargine group suggests the patients were not true basal failures at randomization. While switching to BIAsp 30 improves glycemic control in this patient population, remaining on basal insulin and optimizing the dose may be equally effective in the short term.

Glucose and insulin do not decrease in a dose-dependent manner after increasing doses of mixed fibers that are consumed in muffins for breakfast

Conventional wisdom suggests that fiber consumption leads to lower postprandial glucose and insulin response. We hypothesized that increasing doses of mixed, viscous fiber would lower glucose and insulin levels in a dose-dependent manner. Healthy men (n = 10) and women (n = 10) with a body mass index of 24 ± 2 (mean ± SEM) participated in this double-blind, crossover study. On 4 separate visits, fasting subjects consumed an approximately 2093 kJ (500 calorie) muffin with 0, 4, 8, or 12 g of mixed fibers. Blood was drawn to measure glucose and insulin at regular intervals throughout a 3-hour test period. Area under the curve (AUC) glucose was significantly lower after 0 g of fiber than after 4, 8, or 12 g of fiber (arbitrary AUC units ± SEM: 25.3 ± 5.2 vs 44.6 ± 7.7, 49.7 ± 7.9, 51.5 ± 6.6, respectively; P < .006). Area under the curve glucose increased with increasing fiber doses (P for trend = .0003). Area under the curve insulin was higher after the 4-g dose than after the 0-, 8-, and 12-g doses (arbitrary AUC units ± SEM: 84.4 ± 8.0 vs 60.1 ± 6.5, 69.4 ± 8.7, 69.7 ± 8.5, respectively; P < .05); it did not change in a dose-dependent manner. Area under the curve glucose and AUC insulin did not correlate with each other. Glucose and insulin did not decrease in a dose-dependent manner after 0, 4, 8, and 12 g of mixed fibers were consumed in muffins for breakfast. The lack of differences was largely based on the individual variation in glucose response. Caution should be used when making general claims about the expected impact of fiber on glucose and insulin levels.

A novel wheat variety with elevated content of amylose increases resistant starch formation and may beneficially influence glycaemia in healthy subjects

BackgroundPrevious studies indicate that elevated amylose content in products from rice, corn, and barley induce lower postprandial glycaemic responses and higher levels of resistant starch (RS). Consumption of slowly digestible carbohydrates and RS has been associated with health benefits such as decreased risk of diabetes and cardiovascular disease.ObjectiveTo evaluate the postprandial glucose and insulin responses in vivo to bread products based on a novel wheat genotype with elevated amylose content (38%).DesignBread was baked from a unique wheat genotype with elevated amylose content, using baking conditions known to promote amylose retrogradation. Included test products were bread based on whole grain wheat with elevated amylose content (EAW), EAW with added lactic acid (EAW-la), and ordinary whole grain wheat bread (WGW). All test breads were baked at pumpernickel conditions (20 hours, 120°C). A conventionally baked white wheat bread (REF) was used as reference. Resistant starch (RS) content was measured in vitro and postprandial glucose and insulin responses were tested in 14 healthy subjects.ResultsThe results showed a significantly higher RS content (on total starch basis) in breads based on EAW than in WGW (p<0.001). Lactic acid further increased RS (p<0.001) compared with both WGW and EAW. Breads baked with EAW induced lower postprandial glucose response than REF during the first 120 min (p<0.05), but there were no significant differences in insulin responses. Increased RS content per test portion was correlated to a reduced glycaemic index (GI) (r= − 0.571, p<0.001).ConclusionsThis study indicates that wheat with elevated amylose content may be preferable to other wheat genotypes considering RS formation. Further research is needed to test the hypothesis that bread with elevated amylose content can improve postprandial glycaemic response.

Premeal Injection of Rapid-Acting Insulin Reduces Postprandial Glycemic Excursions in Type 1 Diabetes

OBJECTIVETo assess the effect of three premeal timings of rapid-acting insulin on postprandial glucose excursions in type 1 diabetes.RESEARCH DESIGN AND METHODSTen subjects participated in a three-way randomized crossover trial. Mean ± SD age was 45.5 ± 12.1 years, A1C was 8.55 ± 1.50%, duration of diabetes was 23.8 ± 7.8 years, and duration of continuous subcutaneous insulin infusion therapy was 8.5 ± 6.1 years. Insulin aspart was administered at 30, 15, or 0 min before mealtime.RESULTSArea under the curve was lower in the −15 stratum (0.41 ± 0.51 mmol/l/min) than that in the −30 stratum (1.89 ± 0.72 mmol/l/min, P = 0.029) and 0 stratum (2.11 ± 0.66 mmol/l/min, P = 0.030). Maximum glucose excursion was lower in the −15 stratum (4.77 ± 0.52 mmol/l) than that in the −30 (6.48 ± 0.76 mmol/l, P = 0.025) and 0 stratum (6.93 ± 0.76 mmol/l, P = 0.022). Peak glucose level was lower in the −15 stratum (9.26 ± 0.72 mmol/l) than that in the −30 stratum (11.74 ± 0.80 mmol/l, P = 0.007) and the 0 stratum (12.29 ± 0.93, P = 0.009). Time spent in the 3.5–10 mmol/l range was higher in the −15 stratum (224.5 ± 25.0 min) than that in the 0 stratum (90.5 ± 23.2 min, P = 0.001). There was no significant difference in occurrence of glucose levels <3.5 mmol/l between strata (P = 0.901).CONCLUSIONSAdministration of rapid-acting insulin analogs 15 min before mealtime results in lower postprandial glucose excursions and more time spent in the 3.5–10.0 mmol/l range, without increased risk of hypoglycemia.

The effect of protease inhibitors derived from potato formulated in a minidrink on appetite, food intake and plasma cholecystokinin levels in humans

Protease inhibitor 2 derived from potato (PI2) is claimed to reduce appetite and food intake, stimulate the satiety hormone cholecystokinin (CCK) and lower postprandial glucose peaks when taken before a meal. However, current literature is inconclusive with regard to its efficacy and mechanism. Furthermore, the potential effect of PI2 on appetite motivational ratings without an immediately following meal has not previously been reported. To comprehensively test the effects of 30 mg PI2 in a minidrink on appetite ratings, subsequent food intake, and plasma CCK and glucose responses. Minidrinks with or without 30 mg PI2 were compared in three separate substudies (A, B and C), each using a two-way, placebo-controlled, balanced-order, cross-over design and 23 or 24 subjects (mean over groups: body mass index 25.0 kg m(-2), range 22.5-30.7 kg m(-2); age 41.3, range 18-62 years). The minidrink was given (A) 120 or (B) 30 min before an ad libitum lunch or (C) 30 min before a fixed lunch. Study parameters were self-reported satiety (substudies A and C), ad libitum meal intake (substudies A and B), and (in an n=12 subset) plasma CCK and blood glucose in all substudies. All results were analyzed using analysis of covariance. Protease-inhibitory activity of the PI2-containing minidrinks was assessed under simulated gut conditions. PI2 did not differ from control for any study parameters, in any substudy, despite confirmation of the inhibitory activity of PI2. In this study protease inhibition using PI2 in a minidrink at a dose of 30 mg, as commercially used, had no (functional) efficacy on a range of behavioral and physiological appetite and intake control measures.

REVIEW: Rye Arabinoxylans: Molecular Structure, Physicochemical Properties and Physiological Effects in the Gastrointestinal Tract

ABSTRACTArabinoxylans (AX) are the main dietary fiber (DF) polysaccharides in rye where they represent ≈55% of the total polysaccharides. Rye AX consist of a backbone of (1→4)‐β‐d‐xylopyranosyl residues (X) mainly substituted with α‐l‐arabinofuranosyl residues (A) to varying degrees at the O‐2 position, the O‐3 position, or both. The A/X ratio of total AX is 0.49–0.82 and extractable AX ratio is 0.34–0.85 in different studies. AX also contain small amounts of ferulate residues bound to arabinose as esters at its O‐5 position. The weight average molecular weight varies from 40,000 to 900,000 with an average of ≈200,000. AX influence physiology in different segments of the gastrointestinal tract. The complex molecular structure of rye AX makes them resistant against microbial modification in the small intestine; consequently, rye AX have a much higher influence on the viscosity in the small intestinal digesta than does β‐glucan from oats and barley. In spite of that, it has not been possible in studies with AX‐rich foods such as bread to demonstrate a significant effect on the postprandial glucose response, however, a significantly reduced insulin response has been seen. Nevertheless, addition of 6 g and 12 g of AX‐rich wheat fiber to a breakfast meal has significantly lowered postprandial glucose and insulin response. Studies with hypercholesterolemic pigs fed rye buns rich in AX have resulted in dramatic reductions in plasma total and LDL cholesterol, whereas a gender difference was seen in studies on the effect of AX on plasma lipids in humans. Only certain species of bacteria from the human gut produce the enzymes needed for the degradation of AX. Nevertheless, wheat AX stimulate prebiotic bacteria presumably brought about by cross feeding of lactobacilli and bifidobacteria with degradation products from versatile carbohydrate‐degrading bacteria. Soluble AX are readily fermented in the large intestine, the majority is broken down between the ileum and the cecum. AX, characterized by a low degree of substitution and virtually no doubly substituted xylose, are slowly degraded at more distal locations. The remaining AX, characterized by a high degree of substitution, are not degraded at all. Although the fermentation pattern of AX may vary in different experimental models, in vitro fermentation studies and in vivo intervention studies with animals and humans point to AX as substrates that enhance the formation of butyrate in the large intestine.

Supplementing transglucosidase with a high-fiber diet for prevention of postprandial hyperglycemia in streptozotocin-induced diabetic dogs

Indigestible oligosaccharides have been shown to normalize blood glucose and insulin concentration thereby promoting good health and preventing diseases, such as diabetes. Transglucosidase (TG, alpha-glucosidase, enzyme code (EC) 3.2.1.20) is an enzyme capable of converting starch to oligosaccharides, such as iso-malto-oligosaccharides from maltose, via the action of amylase. The aim of this study was to evaluate whether oral administration of TG with maltose or dextrin is capable of reducing post-prandial serum glucose concentration in experimentally streptozotocin (STZ)-induced diabetic dogs fed on a high-fiber diet. Five healthy and five STZ-induced diabetic dogs were employed in this study. TG supplementation with dextrin or maltose had no detrimental effect in healthy dogs. In fact, TG and dextrin exhibited a flatlined serum glucose pattern, while reducing mean post-prandial serum insulin and glucose concentration as compared to control diet alone. When TG supplementation was tested in STZ-induced diabetic dogs under the context of a high fiber diet, a 13.8% and 23.9% reduction in mean glucose concentration for TG with maltose and dextrin, respectively was observed. Moreover, TG with dextrin resulted in a 13% lower mean post-prandial glucose concentration than TG with maltose, suggesting that dextrin may be a more efficient substrate than maltose when used at the same concentration (1 g/kg). Our results indicate that TG supplementation with diet can lead to lower postprandial glucose levels versus diet alone. However, the efficacy of TG supplementation may depend on the type of diet it is supplemented with. As such, TG administration may be useful for preventing the progression of diabetes mellitus and in its management in dogs.

The Cdc42-interacting Protein-4 (CIP4) Gene Knock-out Mouse Reveals Delayed and Decreased Endocytosis

The newly described F-BAR (Fer/CIP4 and Bin, amphiphysin, Rvs) family of proteins includes Cdc42-interacting protein-4 (CIP4), formin-binding protein-17 (FBP-17) and transactivator of cytoskeletal assembly-1 (Toca-1), and drives membrane deformation and invagination. Membrane remodeling affects endocytosis, vesicle budding, and cargo selection. The F-BAR family presents a novel family of proteins, which little is known about their in vivo function. We investigated the physiological role of CIP4, by creating Cip4-null mice through homologous recombination. Compared with their wild-type littermates, the Cip4-null mice displayed lower early post-prandial glucose levels. Adipocytes isolated from Cip4-null mice exhibited increased [(14)C]2-deoxyglucose uptake compared with cells from wild-type mice. The enhanced insulin sensitivity was not due to higher levels of insulin or phospho-Akt, a critical player in insulin signaling. However, higher glucose transporter 4 (GLUT4) levels were detected in muscle membrane fractions in Cip4-null mice under insulin stimulation. Mouse embryonic fibroblasts from Cip4-null mice demonstrated decreased transferrin uptake, fluorescein isothiocyanate-dextran, and horseradish peroxidase uptake, indicating that CIP4 affects multiple modes of endocytosis. These studies demonstrate a physiological role for CIP4 in endocytosis leading to a whole animal phenotype.

Tagatose: from a sweetener to a new diabetic medication?

Importance of the field: Tagatose is a naturally occurring simple sugar that is a more palatable bulk low-calorie (1.5 kcal/g) sweetener. It was approved as a food additive by the FDA in 2003. Tagatose has been studied as a potential antidiabetic and antiobesity medication. In preliminary studies in humans, tagatose has shown a low postprandial blood glucose and insulin response. Its proposed mechanism of action may involve interference in the absorption of carbohydrates by inhibiting intestinal disaccharidases and glucose transport. It may also act through hepatic inhibition of glycogenolysis.Areas covered in this review: This article summarizes tagatose Phase I and II diabetes trials. It describes the pharmacodynamics and possible mechanism of action of this agent. Literature from 1974 to 2009 is reviewed.What the reader will gain: Better understanding of the implications of postprandial hyperglycemia. An appreciation of the liver as a target of glucose control. Increased awareness of tagatose, a sweetener, as a potential new medication that operates through improvement of postprandial hyperglycemia.Take home message: Tagatose is currently being studied as a postprandial antihyperglycemic agent that may be safer with regard to hypoglycemia. Ongoing Phase III clinical trials will provide more definitive answers.