Type

Journal Article

Authors

Lorraine Brennan
Helen M Roche
Michael J Gibney
Eileen R Gibney
Elaine Drummond
Miriam F Ryan
Aoife M Curran

Subjects

Veterinary

Topics
diabetes mellitus type 2 cell line cell function beta cell pancreatic beta cells waist hip ratio model assessment glucose tolerance test insulin secretion insulin resistance

Uncovering Factors Related to Pancreatic Beta-Cell Function. (2016)

Abstract 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. 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. 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. 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.
Collections Ireland -> University College Dublin -> PubMed
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Ireland -> University College Dublin -> Agriculture and Food Science Research Collection
Ireland -> University College Dublin -> School of Public Health, Physiotherapy and Sports Science
Ireland -> University College Dublin -> College of Health and Agricultural Sciences
Ireland -> University College Dublin -> Conway Institute
Ireland -> University College Dublin -> Public Health, Physiotherapy and Sports Science Research Collection
Ireland -> University College Dublin -> Conway Institute
Ireland -> University College Dublin -> School of Public Health, Physiotherapy and Sports Science
Ireland -> University College Dublin -> School of Agriculture and Food Science
Ireland -> University College Dublin -> Public Health, Physiotherapy and Sports Science Research Collection
Ireland -> University College Dublin -> Conway Institute Research Collection
Ireland -> University College Dublin -> Conway Institute Research Collection
Ireland -> University College Dublin -> School of Agriculture and Food Science
Ireland -> University College Dublin -> College of Health and Agricultural Sciences
Ireland -> University College Dublin -> Agriculture and Food Science Research Collection
Ireland -> University College Dublin -> Institutes and Centres

Full list of authors on original publication

Lorraine Brennan, Helen M Roche, Michael J Gibney, Eileen R Gibney, Elaine Drummond, Miriam F Ryan, Aoife M Curran

Experts in our system

1
Lorraine Brennan
University College Dublin
Total Publications: 166
 
2
Helen M. Roche
University College Dublin
Total Publications: 105
 
3
Michael J Gibney
University College Dublin
Total Publications: 102
 
4
Eileen R Gibney
University College Dublin
Total Publications: 98
 
5
Elaine Drummond
University College Dublin
Total Publications: 4
 
6
Miriam Ryan
University College Dublin
Total Publications: 34