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Abstract Background Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. Methods Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. Results Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = −0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = −0.34, P = 0.012) and dinner (r = −0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. Conclusions In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.

Introduction: Reference ranges for determining pathological versus normal postoperative return of bowel function are not well characterised for general surgery patients. This study aimed to characterise time to first postoperative passage of stool after general surgery; determine associations between clinical factors and delayed time to first postoperative stool; and evaluate the association between delay to first postoperative stool and prolonged length of hospital stay. Methods: This study included consecutive admissions at two tertiary hospitals across a two-year period whom underwent a range of general surgery operations. Multivariable logistic regression analyses were conducted to determine associations between the explanatory variables and delayed first postoperative stool, and between delayed first postoperative stool and length of hospital stay. The previously specified explanatory variables were used, with the addition of the dichotomised ≥4-day delay to first postoperative stool. Prolonged length of hospital stay was considered ≥7 days. Results: 2,212 general surgery patients were included. Median time to first postoperative stool was 2.28 (IQR 1.06–3.96). Median length of stay was 7.19 (IQR 4.50–12.01). Several operative characteristics and medication exposures were associated with delayed first postoperative stool. There was a statistically significant association between delayed first postoperative stool (≥4 days) and prolonged length of stay (≥7 days) (OR 4.34, 95 %CI 3.27 to 5.77, p

Abstract Background Caloric supplements are increasingly used by older people, aiming to increase their daily protein intake. These high caloric drinks, rich in glucose and whey-protein in particular, may result in potential harmful decreases in blood pressure (BP). The effect of ingesting whey-protein with glucose and fat on BP is unknown. It has also been assumed that the maximum fall in systolic blood pressure occurs within 2 h of a meal. Methods This study aimed to determine in older men, the effects of whey-protein, alone and mixed with other macronutrients, on systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) in older men for 3 h. Thirteen older men (age 75 ± 2yrs; body mass index (BMI) 25.6 ± 0.6 kg/m2) ingested a drink on separate study days: (i) 70 g whey-protein (P280); (ii) 14 g whey-protein, 28 g carbohydrate, 12.4 g fat (M280); (iii) 70 g whey-protein, 28 g carbohydrate, 12.4 g fat (M504); or (iv) a non-caloric control drink (C). Results SBP decreased after all three nutrient drinks compared to the C, with the greatest reduction after the M504 drink (P = 0.008). Maximal decreases in SBP (C: -14 ± 2 mmHg, P280: -22 ± 2 mmHg, M280: -22 ± 4 mmHg, M504: -24 ± 3 mmHg) occurred about 2 h after drink ingestion and this fall was sustained thereafter (120-180 min: P280 and M504 vs. C P

Abstract Background The rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D). Methods Twelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m2) received, on three separate occasions, 3 g (‘Trp-3’) or 1.5 g (‘Trp-1.5’) tryptophan, or control (0.9% saline), intragastrically, in randomised, double-blind fashion, 30 min before a mixed-nutrient drink (500 kcal, 74 g carbohydrates), containing 3 g 3-O-methyl-D-glucose (3-OMG) to assess glucose absorption. Venous blood samples were obtained at baseline, after tryptophan, and for 2 h post-drink for measurements of plasma glucose, C-peptide, glucagon and 3-OMG. Gastric emptying of the drink was quantified using two-dimensional ultrasound. Results Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15–30 min and from t = 30–45 min compared with control and Trp-1.5, respectively (both P

Abstract Background Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. Objectives To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. Methods EMA is a population-based, nested case–control study which linked archived maternal serum samples collected during weeks 15–19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency’s Air Quality System data using the maternal residential address reported during the prenatal screening visit. Results Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from − 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. Conclusion This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring.

Background: Gastrointestinal symptoms have been reported to occur frequently in diabetes, but their prevalence in Chinese community-dwelling individuals with diabetes is unknown. The present study aimed to address this issue and explore the risk factors for gastrointestinal symptoms. Methods: A total of 1304 community-dwelling participants (214 with diabetes, 360 with prediabetes and 730 with normoglycemia) were surveyed for gastrointestinal symptoms using the Diabetes Bowel Symptom Questionnaire. Logistic regression analyses were applied to identify risk factors for gastrointestinal symptoms. Results: Of the overall study population, 18.6% reported at least one gastrointestinal symptom, without a significant difference between subjects with normoglycemia (17.7%), prediabetes (19.7%) and diabetes (20.1%). In all three groups, lower gastrointestinal symptoms, particularly diarrhea and constipation, were the most frequent. There was an interaction between age (≥65 years) and diabetes on the prevalence of at least one gastrointestinal symptom (p = 0.01) and of constipation (p = 0.004), with these being most frequent in subjects with diabetes aged ≥ 65 years. After multivariable adjustment, female gender and older age were associated with increased odds of at least one gastrointestinal symptom, specifically lower gastrointestinal symptoms. Older age was also associated with an increase in upper gastrointestinal symptoms. Conclusions: Gastrointestinal symptoms are common in Chinese community-dwelling adults with and without diabetes. Females, and the elderly with diabetes, are at an increased risk of symptoms.

The ingestion of dietary protein with, or before, carbohydrate may be a useful strategy to reduce postprandial hyperglycemia, but its effect in older people, who have an increased predisposition for type 2 diabetes, has not been clarified. Blood glucose, plasma insulin and glucagon concentrations were measured for 180 min following a drink containing either glucose (120 kcal), whey-protein (120 kcal), whey-protein plus glucose (240 kcal) or control (~2 kcal) in healthy younger (n = 10, 29 ± 2 years; 26.1 ± 0.4 kg/m2) and older men (n = 10, 78 ± 2 years; 27.3 ± 1.4 kg/m2). Mixed model analysis was used. In both age groups the co-ingestion of protein with glucose (i) markedly reduced the increase in blood glucose concentrations following glucose ingestion alone (p < 0.001) and (ii) had a synergistic effect on the increase in insulin concentrations (p = 0.002). Peak insulin concentrations after protein were unaffected by ageing, whereas insulin levels after glucose were lower in older than younger men (p < 0.05) and peak insulin concentrations were higher after glucose than protein in younger (p < 0.001) but not older men. Glucagon concentrations were unaffected by age. We conclude that the ability of whey-protein to reduce carbohydrate-induced postprandial hyperglycemia is retained in older men and that protein supplementation may be a useful strategy in the prevention and management of type 2 diabetes in older people.

Postprandial hypotension (PPH) occurs frequently in older people >65 years old. Protein-rich supplements, particularly whey protein (WP), are increasingly used by older people for various health benefits. We have reported that 70 g WP drinks cause significant, and in some cases marked, falls in blood pressure (BP) in older men. The effects of lower, more widely used, doses (~30 g) on systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) are not known. In a randomized order, eight older men (age: 72 ± 1 years; body mass index (BMI): 25 ± 1 kg/m2) after overnight fast ingested a drink containing (i) a non-caloric control (~2 kcal), (ii) 30 g of whey protein (120 kcal; ‘WP30’), or (iii) 70 g of whey protein (280 kcal; ‘WP70’). The BP and HR were measured in this pilot study with an automated device before and at 3-min intervals for 180 min following drink ingestion. Drink condition effects were determined by repeated-measures ANOVA. The SBP decreased after both WP drinks compared to the control (p = 0.016), particularly between 120 and 180 min, with no difference in the effects of WP30 and WP70. The SBP decreased by ≥20 mmHg in more than 50% of people after both WP drinks (WP30: 63%; WP70: 75%) compared to 38% after the control. The maximum fall in the SBP occurred during the third hour, with the nadir occurring latest after WP70. The DBP decreased non-significantly by several mmHg more after the WP drinks than after the control. The maximum HR increases occurred during the third hour, with the greatest increase after WP70. The SBP decreased after both WP drinks compared to the control, with the effects most evident between 120 and 180 min. Accordingly, ingestion of even relatively modest protein loads in older men has the potential to cause PPH.

Postprandial glycemic control is an important target for optimal type 2 diabetes management, but is often difficult to achieve. The gastrointestinal tract plays a major role in modulating postprandial glycaemia in both health and diabetes. The various strategies that have been proposed to modulate gastrointestinal function, particularly by slowing gastric emptying and/or stimulating incretin hormone GLP-1, are summarized in this review.

The interaction of nutrients with the small intestine modulates postprandial cardiovascular function. Rapid small intestinal nutrient delivery may reduce blood pressure markedly, particularly in patients with type 2 diabetes (T2DM). Postprandial hypotension occurs in ~30% of patients with longstanding T2DM, but there is little information about the cardiovascular effects of different macronutrients. We compared the blood pressure and heart rate responses to standardized intraduodenal glucose and fat infusions in T2DM. Two parallel groups, including 26 T2DM patients who received intraduodenal glucose infusion and 14 T2DM patients who received intraduodenal fat, both at 2 kcal/min over 120 min, were compared retrospectively. Blood pressure and heart rate were measured at regular intervals. Systolic blood pressure was stable initially and increased slightly thereafter in both groups, without any difference between them. Diastolic blood pressure decreased in response to intraduodenal glucose, but remained unchanged in response to lipid, with a significant difference between the two infusions (P = 0.04). Heart rate increased during both intraduodenal glucose and lipid infusions (P < 0.001 each), and the increment was greater in response to intraduodenal fat than glucose (P = 0.004). In patients with T2DM, intraduodenal fat induced a greater increase in heart rate, associated with a diminished reduction in blood pressure, when compared with isocaloric glucose. The macronutrient composition of meals may be an important consideration in T2DM patients with symptomatic postprandial hypotension.

Abstract Background The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. Methods This is the first genetic study of > 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h 2 g ) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. Results We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. Conclusions Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders.

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

Metformin, the most widely prescribed drug therapy for type 2 diabetes, has pleiotropic benefits, in addition to its capacity to lower elevated blood glucose levels, including mitigation of cardiovascular risk. The mechanisms underlying the latter remain unclear. Mechanistic studies have, hitherto, focused on the direct effects of metformin on the heart and vasculature. It is now appreciated that effects in the gastrointestinal tract are important to glucose-lowering by metformin. Gastrointestinal actions of metformin also have major implications for cardiovascular function. This review summarizes the gastrointestinal mechanisms underlying the action of metformin and their potential relevance to cardiovascular benefits.

Ageing is associated with changes in feeding behavior. We have reported that there is suppression of energy intake three hours after whey protein drink ingestion in young, but not older, men. This study aimed to determine these effects over a time period of 9 h. Fifteen younger (27 ± 1 years, 25.8 ± 0.7 kg/m2) and 15 older (75 ± 2 years, 26.6 ± 0.8 kg/m2) healthy men were studied on three occasions on which they received, in a randomized order, a 30 g/120 kcal, 70 g/280 kcal whey-protein, or control (~2 kcal) drink. Ad-libitum energy intake (sum of breakfast, lunch, and dinner) was suppressed in a protein load responsive fashion (P = 0.001). Suppression was minimal at breakfast, substantial at lunch (~−16%, P = 0.001), no longer present by dinner, and was less in older than younger men (−3 ± 4% vs. −8 ± 4%, P = 0.027). Cumulative protein intake was increased in the younger and older men (+20% and +42%, P < 0.001). Visual analogue scale ratings of fullness were higher and desire to eat and prospective food consumption were lower after protein vs. control, and these effects were smaller in older vs. younger men (interaction effect P < 0.05). These findings support the use of whey-protein drink supplements in older people who aim to increase their protein intake without decreasing their overall energy intake.

It is now widely appreciated that gastrointestinal function is central to the regulation of metabolic homeostasis. Following meal ingestion, the delivery of nutrients from the stomach into the small intestine (i.e., gastric emptying) is tightly controlled to optimise their subsequent digestion and absorption. The complex interaction of intraluminal nutrients (and other bioactive compounds, such as bile acids) with the small and large intestine induces the release of an array of gastrointestinal hormones from specialised enteroendocrine cells (EECs) distributed in various regions of the gut, which in turn to regulate gastric emptying, appetite and postprandial glucose metabolism. Stimulation of gastrointestinal hormone secretion, therefore, represents a promising strategy for the management of metabolic disorders, particularly obesity and type 2 diabetes mellitus (T2DM). That EECs are distributed distinctively between the proximal and distal gut suggests that the region of the gut exposed to intraluminal stimuli is of major relevance to the secretion profile of gastrointestinal hormones and associated metabolic responses. This review discusses the process of intestinal digestion and absorption and their impacts on the release of gastrointestinal hormones and the regulation of postprandial metabolism, with an emphasis on the differences between the proximal and distal gut, and implications for the management of obesity and T2DM.

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = −0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.

Protein-rich supplements are used commonly to increase energy intake in undernourished older people. This study aimed to establish age effects on energy intake, appetite, gastric emptying, blood glucose, and gut hormones in response to protein-rich drinks. In a randomized double-blind, order, 13 older men (age: 75 ± 2 yrs, body mass index (BMI): 26 ± 1 kg/m2) and 13 younger (23 ± 1 yrs, 24 ± 1 kg/m2) men consumed (i) a control drink (~2 kcal) or drinks (450 mL) containing protein/fat/carbohydrate: (ii) 70 g/0 g/0 g (280 kcal/‘P280′), (iii) 14 g/12.4 g/28 g (280 kcal/‘M280′), (iv) 70 g/12.4 g/28 g (504 kcal/‘M504′), on four separate days. Appetite (visual analog scales), gastric emptying (3D ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) concentrations (0–180 min), and ad-libitum energy intake (180–210 min) were determined. Older men, compared to younger men, had higher fasting glucose and CCK concentrations and lower fasting GLP-1 concentrations (all p < 0.05). Energy intake by P280 compared to control was less suppressed in older men (increase: 49 ± 42 kcal) than it was in younger men (suppression: 100 ± 54 kcal, p = 0.038). After the caloric drinks, the suppression of hunger and the desire to eat, and the stimulation of fullness was less (p < 0.05), and the stimulation of plasma GLP-1 was higher (p < 0.05) in older men compared to younger men. Gastric emptying, glucose, insulin, ghrelin, and CCK responses were similar between age groups. In conclusion, ageing reduces the responses of caloric drinks on hunger, the desire to eat, fullness, and energy intake, and protein-rich nutrition supplements may be an effective strategy to increase energy intake in undernourished older people.

A whey protein/guar gum preload reduces postprandial glycaemia in type 2 diabetes through slowing gastric emptying. However, gastric emptying has previously been assessed using a stable isotope breath test technique, which cannot discriminate between slowing of gastric emptying and small intestinal absorption. This preload also may be useful in the management of postprandial hypotension. We evaluated the effects of a whey protein/guar preload on gastric emptying, glucose absorption, glycaemic/insulinaemic and blood pressure (BP) responses to an oral glucose load. Eighteen healthy older participants underwent measurements of gastric emptying (scintigraphy), plasma glucose and insulin, glucose absorption, superior mesenteric artery (SMA) flow, BP and heart rate (HR) after ingesting a 50 g glucose drink, with or without the preload. The preload reduced plasma glucose (p = 0.02) and serum 3-O-methylglucose (3-OMG) (p = 0.003), and increased plasma insulin (p = 0.03). There was no difference in gastric emptying or BP between the two days. The reduction in plasma glucose on the preload day was related to the reduction in glucose absorption (r = 0.71, p = 0.002). In conclusion, the glucose-lowering effect of the preload may relate to delayed small intestinal glucose absorption and insulin stimulation, rather than slowing of gastric emptying.

Postprandial hypotension (PPH) is under-recognised, but common, particularly in the elderly, and is of clear clinical importance due to both the independent association between PPH and an increase in mortality and lack of effective management for this condition. Following health concerns surrounding excessive consumption of sugar, there has been a trend in the use of low- or non-nutritive sweeteners as an alternative. Due to the lack of literature in this area, we conducted a systematic search to identify studies relevant to the effects of different types of sweeteners on postprandial blood pressure (BP). The BP response to ingestion of sweeteners is generally unaffected in healthy young subjects, however in elderly subjects, glucose induces the greatest decrease in postprandial BP, while the response to sucrose is less pronounced. The limited studies investigating other nutritive and non-nutritive sweeteners have demonstrated minimal or no effect on postprandial BP. Dietary modification by replacing high nutritive sweeteners (glucose, fructose, and sucrose) with low nutritive (d-xylose, xylitol, erythritol, maltose, maltodextrin, and tagatose) and non-nutritive sweeteners may be a simple and effective management strategy for PPH.

Whey protein, when ingested on its own, load-dependently slows gastric emptying and stimulates gut hormone concentrations in healthy young men. The aim of this study was to determine the effects of substitution, and addition, of carbohydrate (dextrose) and fat (olive oil) to whey protein. In randomized, double-blind order, 13 healthy young men (age: 23 ± 1 years, body mass index: 24 ± 1 kg/m2) ingested a control drink (450 mL; ~2 kcal/‘control’) or iso-volumetric drinks containing protein/carbohydrate/fat: (i) 14 g/28 g/12.4 g (280 kcal/‘M280′), (ii) 70 g/28 g/12.4 g (504kcal/‘M504′), and (iii) 70 g/0 g/0 g (280 kcal/‘P280′), on 4 separate study days. Gastric emptying (n = 11, 3D-ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) concentrations (0–180 min), appetite (visual analogue scales), and ad-libitum buffet-meal energy intake (180–210 min) were determined. Substitution of protein with carbohydrate and fat was associated with faster gastric emptying (lower 50% emptying time (T50)), reduced suppression of ghrelin, and stimulation of GLP-1 (all P < 0.001); while the addition of carbohydrate and fat to protein did not affect gastric emptying or gut hormone responses significantly. Total energy intake (i.e., drink plus meal) was greater after all caloric drinks than control (P < 0.001). In conclusion, substitution of whey protein with dextrose and olive oil accelerated gastric emptying. Higher protein content of a mixed macronutrient drink increased gut hormone and insulin responses.

Glutamine is a potent stimulus for the release of glucagon-like peptide-1, which increases postprandial insulin and slows gastric emptying (GE). We determined the effects of glutamine on GE of, and glycaemic responses to, low- and high-nutrient drinks in eight healthy males (mean age 21.6 ± 0.7 years and BMI 22.9 ± 0.7 kg/m2). Participants were studied on four occasions on which they consumed either a low-nutrient (beef soup; 18 kcal) or high-nutrient (75 g dextrose; 255 kcal) drink, each with or without 30 g of glutamine (120 kcal), in a randomised, crossover design. GE (2D ultrasound), blood glucose and plasma insulin concentrations were measured concurrently. Glutamine slowed GE (half emptying time (T50)) of both low- (45 ± 3 min vs. 26 ± 2 min, p < 0.001), and high-nutrient, (100 ± 5 min vs. 77 ± 5 min, p = 0.03) drinks, however, there was no effect on GE of the high nutrient drinks when expressed as kcal/min (3.39 ± 0.21 kcal/min vs. 3.81 ± 0.20 kcal/min, p = 0.25). There was no change in blood glucose after the low-nutrient drinks with or without glutamine, despite a slight increase in plasma insulin with glutamine (p = 0.007). The rise in blood glucose following the high-nutrient drink (p = 0.0001) was attenuated during the first 60 min by glutamine (p = 0.007). We conclude that in healthy subjects, glutamine slows GE of both low- and high-nutrient drinks comparably and attenuates the rise in blood glucose after the high-nutrient glucose drink.

Protein-rich supplements are used widely for the management of malnutrition in the elderly. We reported previously that the suppression of energy intake by whey protein is less in older than younger adults. The aim was to determine the effects of substitution, and adding of carbohydrate and fat to whey protein, on ad libitum energy intake from a buffet meal (180–210 min), gastric emptying (3D-ultrasonography), plasma gut hormone concentrations (0–180 min) and appetite (visual analogue scales), in healthy older men. In a randomized, double-blind order, 13 older men (75 ± 2 years) ingested drinks (~450 mL) containing: (i) 70 g whey protein (280 kcal; ‘P280’); (ii) 14 g protein, 28 g carbohydrate, 12.4 g fat (280 kcal; ‘M280’); (iii) 70 g protein, 28 g carbohydrate, 12.4 g fat (504 kcal; ‘M504’); or (iv) control (~2 kcal). The caloric drinks, compared to a control, did not suppress appetite or energy intake; there was an increase in total energy intake (drink + meal, p < 0.05), which was increased most by the M504-drink. P280- and M504-drink ingestion were associated with slower a gastric-emptying time (n = 9), lower ghrelin, and higher cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) than M280 (p < 0.05). Glucose and insulin were increased most by the mixed-macronutrient drinks (p < 0.05). In conclusion, energy intake was not suppressed, compared to a control, and particularly whey protein, affected gastric emptying and gut hormone responses.

Ectopic expression of key reprogramming transgenes in somatic cells enables them to adopt the characteristics of pluripotency. Such cells have been termed induced pluripotent stem (iPS) cells and have revolutionized the field of somatic cell reprogramming, as the need for embryonic material is obviated. One of the issues facing both the clinical translation of iPS cell technology and the efficient derivation of iPS cell lines in the research laboratory is choosing the most appropriate somatic cell type for induction. In this study, we demonstrate the direct reprogramming of a defined population of neural stem cells (NSCs) derived from the subventricular zone (SVZ) and adipose tissue-derived cells (ADCs) from adult mice using retroviral transduction of the Yamanaka factors Oct4, Sox2, Klf4, and c-Myc, and compared the results obtained with a mouse embryonic fibroblast (mEF) control. We isolated mEFs, NSCs, and ADCs from transgenic mice, which possess a GFP transgene under control of the Oct4 promoter, and validated GFP expression as an indicator of reprogramming. While transduction efficiencies were not significantly different among the different cell types (mEFs 68.70 ± 2.62%, ADCs 70.61 ± 15.4%, NSCs, 68.72 ± 3%, p = 0.97), the number of GFP-positive colonies and hence the number of reprogramming events was significantly higher for both NSCs (13.50 ± 4.10 colonies, 0.13 ± 0.06%) and ADCs (118.20 ± 38.28 colonies, 1.14 ± 0.77%) when compared with the mEF control (3.17 ± 0.29 colonies, 0.03 ± 0.005%). ADCs were most amenable to reprogramming with an 8- and 38-fold greater reprogramming efficiency than NSCs and mEFs, respectively. Both NSC iPS and ADC iPS cells were demonstrated to express markers of pluripotency and could differentiate to the three germ layers, both in vitro and in vivo, to cells representative of the three germ lineages. Our findings confirm that ADCs are an ideal candidate as a readily accessible somatic cell type for high efficiency establishment of iPS cell lines.