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  • Publication
    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.
      333Scopus© Citations 4
  • Publication
    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.
      291Scopus© Citations 6