Effects of a casein hydrolysate versus intact casein on gastric emptying and amino acid responses.

PURPOSE: Milk proteins and/or their hydrolysates have been reported to have beneficial effects for improving postprandial glycaemia. Gastric emptying is a major determinant of postprandial glycaemia, yet limited studies have examined the effects of intact milk proteins compared to hydrolysates on gastric emptying. We investigated gastric emptying of a casein hydrolysate compared to intact casein. METHODS: Nine overweight and obese adults (mean ± SD age: 59.5 ± 6.5 years and BMI 28.4 ± 2.6 kg/m2) were studied in a randomised crossover design. Gastric emptying was assessed by paracetamol absorption test, with HPLC-MS being used for determining paracetamol and its primary metabolites in plasma. Glucose, insulin and amino acid responses were also assessed. RESULTS: Linear mixed model analysis showed no effect of treatment [F(1, 55) = 2.1, P = 0.16] or treatment × time interactions [F(6, 54) = 1.5, P = 0.21] for paracetamol concentrations. In addition, there were no significant differences between the intact casein and hydrolysate for any of the gastric emptying outcome measures (Cmax, AUC0-30min, AUC0-60min; AUC0-240min). However, insulin was increased in the early postprandial period (iAUC0-15min, iAUC0-30min;P < 0.05) and there was a treatment effect for glucose [F(1, 53) = 5.3, P = 0.03] following the casein hydrolysate compared to intact casein. No significant differences in amino acids were found between the two conditions. CONCLUSIONS: Gastric emptying of a casein hydrolysate compared to intact casein does not differ. Mechanisms other than gastric emptying, for example the presence of a bioactive peptide sequence, may contribute to the glycaemic management effects of certain milk protein hydrolysates and warrant further investigation.

A proteomic signature that reflects pancreatic beta-cell function.

AIM: Proteomics has the potential to enhance early identification of beta-cell dysfunction, in conjunction with monitoring the various stages of type 2 diabetes onset. The most routine method of assessing pancreatic beta-cell function is an oral glucose tolerance test, however this method is time consuming and carries a participant burden. The objectives of this research were to identify protein signatures and pathways related to pancreatic beta-cell function in fasting blood samples. METHODS: Beta-cell function measures were calculated for MECHE study participants who completed an oral glucose tolerance test and had proteomic data (n = 100). Information on 1,129 protein levels was obtained using the SOMAscan assay. Receiver operating characteristic curves were used to assess discriminatory ability of proteins of interest. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Replication of findings were achieved in a second human cohort where possible. RESULTS: Twenty-two proteins measured by aptamer technology were significantly associated with beta-cell function/HOMA-IR while 17 proteins were significantly associated with the disposition index (p ≤ 0.01). Receiver operator characteristic curves determined the protein panels to have excellent discrimination between low and high beta-cell function. Linear regression analysis determined that beta-endorphin and IL-17F have strong associations with beta-cell function/HOMA-IR, ß = 0.039 (p = 0.005) and ß = -0.027 (p = 0.013) respectively. Calcineurin and CRTAM were strongly associated with the disposition index (ß = 0.005 and ß = 0.005 respectively, p = 0.012). In vitro experiments confirmed that IL-17F modulated insulin secretion in the BRIN-BD11 cell line, with the lower concentration of 10 ng/mL significantly increasing glucose stimulated insulin secretion (p = 0.043). CONCLUSIONS: Early detection of compromised beta-cell function could allow for implementation of nutritional and lifestyle interventions before progression to type 2 diabetes.

Casein Hydrolysate with Glycemic Control Properties: Evidence from Cells, Animal Models, and Humans.

Evidence exists to support the role of dairy derived proteins whey and casein in glycemic management. The objective of the present study was to use a cell screening method to identify a suitable casein hydrolysate and to examine its ability to impact glycemia related parameters in an animal model and in humans. Following screening for the ability to stimulate insulin secretion in pancreatic beta cells, a casein hydrolysate was selected and further studied in the ob/ob mouse model. An acute postprandial study was performed in 62 overweight and obese adults. Acute and long-term supplementation with the casein hydrolysate in in vivo studies in mice revealed a glucose lowering effect and a lipid reducing effect of the hydrolysate (43% reduction in overall liver fat). The postprandial human study revealed a significant increase in insulin secretion ( p = 0.04) concomitant with a reduction in glucose ( p = 0.03). The area under the curve for the change in glucose decreased from 181.84 ± 14.6 to 153.87 ± 13.02 ( p = 0.009). Overall, the data supports further work on the hydrolysate to develop into a functional food product.

Uncovering Factors Related to Pancreatic Beta-Cell Function.

AIM: The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i) to identify factors related to pancreatic beta-cell function and (ii) to perform mechanistic studies in vitro. METHODS: Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolerance test as part of the Metabolic Challenge Study. Anthropometric and biochemical parameters were assessed as potential modulators of beta-cell function. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Validation of findings were performed in a second human cohort. RESULTS: Waist-to-hip ratio was the strongest anthropometric modulator of beta-cell function, with beta-coefficients of -0.33 (p = 0.001) and -0.30 (p = 0.002) for beta-cell function/homeostatic model assessment of insulin resistance (HOMA-IR), and disposition index respectively. Additionally, the resistin-to-adiponectin ratio (RA index) emerged as being strongly associated with beta-cell function, with beta-coefficients of -0.24 (p = 0.038) and -0.25 (p = 0.028) for beta-cell function/HOMA-IR, and disposition index respectively. Similar results were obtained using a third measure for beta-cell function. In vitro experiments revealed that the RA index was a potent regulator of acute insulin secretion where a high RA index (20ng ml-1 resistin, 5nmol l-1 g-adiponectin) significantly decreased insulin secretion whereas a low RA index (10ng ml-1 resistin, 10nmol l-1 g-adiponectin) significantly increased insulin secretion. The RA index was successfully validated in a second human cohort with beta-coefficients of -0.40 (p = 0.006) and -0.38 (p = 0.008) for beta-cell function/ HOMA-IR, and disposition index respectively. CONCLUSIONS: Waist-to-hip ratio and RA index were identified as significant modulators of beta-cell function. The ability of the RA index to modulate insulin secretion was confirmed in mechanistic studies. Future work should identify strategies to alter the RA index.

Bioavailability of milk protein-derived bioactive peptides: a glycaemic management perspective.

Milk protein-derived peptides have been reported to have potential benefits for reducing the risk of type 2 diabetes. However, what the active components are and whether intact peptides exert this bioactivity has received little investigation in human subjects. Furthermore, potentially useful bioactive peptides can be limited by low bioavailability. Various peptides have been identified in the gastrointestinal tract and bloodstream after milk-protein ingestion, providing valuable insights into their potential bioavailability. However, these studies are currently limited and the structure and sequence of milk peptides exerting bioactivity for glycaemic management has received little investigation in human subjects. The present article reviews the bioavailability of milk protein-derived peptides in human studies to date, and examines the evidence on milk proteins and glycaemic management, including potential mechanisms of action. Areas in need of advancement are identified. Only by establishing the bioavailability of milk protein-derived peptides, the active components and the mechanistic pathways involved can the benefits of milk proteins for the prevention or management of type 2 diabetes be fully realised in future.

An in vivo study examining the antiinflammatory effects of chamomile, meadowsweet, and willow bark in a novel functional beverage.

The antioxidant and antiinflammatory properties of polyphenols are well documented in vitro but there are few human studies. A herbal beverage composed of chamomile, meadowsweet, and willow bark (CMW) was developed and tested for its antiinflammatory effect in a cohort of healthy adults (n = 20) during a 4-week intervention. Subjects were randomised to either the treatment (TG) or placebo group (PG). The three herbs under study, which have been used in traditional and alternative medicine, were delivered in a berry extract matrix. This berry extract was used as a control in the experiment. The objective was to assess the herbs' effects on systemic inflammation and joint function by examining circulating cytokines and mechanical joint flexibility. Blood serum was analyzed for cytokines IL-1ß, IL-6, and TNFα. There was an average decrease of 21.7% IL-1ß in the treatment group, whereas the decrease seen in the placebo group was 3% but these were not statistically significant. Quartile analysis based on baseline production of TNFα demonstrated a decrease in the treatment group's IL-6 levels. This group showed improvements in mechanical joint function and pain upon movement of joints specific to the knee and lower back. Overall, no significant antiinflammatory effects were seen. The evidence is therefore inconclusive and further investigations are required using a larger cohort with some degree of elevated inflammatory activity.

Antioxidant and pro-apoptotic effects of marine-derived, multi-mineral aquamin supplemented with a pine bark extract, Enzogenol, and a green tea extract, Sunphenon.

A high dietary intake of polyphenols has been associated with a decreased risk of cardiovascular disease and cancer, attributed in part to their antioxidant activity and pro-apoptotic effects. Aquamin is a multi-mineral algal extract that enhances bone mineralization, relieves osteoarthritis, and aids digestion; however, Aquamin has not demonstrated antioxidant activity. In the present study, Aquamin was supplemented with 8% Enzogenol, a pine bark extract with a high phenolic content, and 2% Sunphenon, a green tea extract that also has a high phenolic content to produce a mixed product (A:E:S). The antioxidant activity of A:E:S was compared with that of its constituent compounds and also with catechin and epigallocatechin by measuring total phenol content, ferric-reducing antioxidant potential, and 2,2-diphenyl-2-picrylhydrazyl hydrate. The cytotoxic and apoptotic effects of the compounds were also measured in the U937, human monocytic blood cell line. A:E:S demonstrated an antioxidant activity that was equal to that of the compounds used in its preparation. Aquamin was not cytotoxic in the U937 cell line; however, A:E:S was cytotoxic and the primary mechanism of cell death was apoptosis. The biological effects of Aquamin were enhanced by supplementation with Enzogenol and Sunphenon to include antioxidant effects and the ability to induce apoptosis in U937 cells.

Epigenetic regulation in obesity.

PURPOSE OF REVIEW: Research suggests that 65% of variation in obesity is genetic. However, much of the known genetic associations have little known function and their effect size small, thus the gene-environment interaction, including epigenetic influences on gene expression, is suggested to be an important factor in the susceptibilty to obesity. This review will explore the potential of epigenetic markers to influence expression of genes associated with obesity. RECENT FINDINGS: Epigenetic changes in utero are known to have direct implications on the phenotype of the offspring. More recently work has focused on how such epigenetic changes continue to regulate risk of obesity from infancy through to adulthood. Work has shown that, for example, hypomethylation of the MC4 gene causes an increase in expression, and has a direct impact on appetite and intake, and thus influences risk of obesity. Similar influences are also seen in other aspects of obesity including inflammation and adiposity. SUMMARY: Maternal diet during foetal development has many epigenetic implications, which affect the offspring's risk factors for obesity during childhood and adulthood, and even in subsequent generations. Genes associated with risk of obesity, are susceptible to epigenetic mutations, which have subsequent effects on disease mechanisms, such as appetite and impaired glucose and insulin tolerance.

Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark.

Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0-100 µM) were incubated with THP1 macrophages, and interleukin (IL)-1ß, IL-6 and tumour necrosis factor-alpha (TNF-α) were measured. At concentrations of 10 µM, both apigenin and quercetin reduced IL-6 significantly ( p < 0.05). Apigenin at 10 µM and quercetin at 25 µM reduced TNF-α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL-6 and TNF-α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts.

Cancer information needs of people with intellectual disability: a review of the literature.

The lifespan of people with an intellectual disability has increased significantly in recent years; however, this has resulted in a rising incidence of age-related illnesses including cancer. The World Health Organisation has expressed concern as evidence suggests prevalence rates for cancer are increasing for this group. The needs of people with a cancer diagnosis and an intellectual disability are beginning to be highlighted; however, there appears to be a substantial dearth of services including appropriate cancer information. This presents alarming obstacles and barriers to high-quality cancer care impacting on treatment, management and overall survival rates for this client group. Furthermore, a number of policy and research reports directed at the health needs of people with an intellectual disability have continually highlighted the need for accessible information and effective communication. Having access to cancer information should be considered a crucial part of providing optimum holistic care for this client group. Cancer professionals should assess the unique information needs of people with an intellectual disability as mainstream information does not meet their requirements. Furthermore, health professionals working in intellectual disability settings must also address their knowledge and information deficits in this regard. This paper presents a review of the literature with a specific focus on the cancer information needs of people with an intellectual disability.