title: Uncovering Factors Related to Pancreatic Beta-Cell Function.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Republic of Ireland.
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Curran
authors.affiliation: Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Republic of Ireland.
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Ryan
authors.affiliation: Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Republic of Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: Drummond
authors.affiliation: Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Republic of Ireland.
authors.forename: Eileen R
authors.initials: ER
authors.lastname: Gibney
authors.affiliation: Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Republic of Ireland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gibney
authors.affiliation: Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Republic of Ireland.|Nutrigenomics Research Group, UCD Conway Institute of Biomolecular and Biomedical Research and UCD Institute of Food and Health, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Belfield, Dublin 4, Republic of Ireland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.affiliation: Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Republic of Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000886:Anthropometry; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008564:Membrane Potentials; D052243:Resistin / Q000378:metabolism
chemical_list: D052242:Adiponectin; D007328:Insulin; D052243:Resistin