Uncovering Factors Related to Pancreatic Beta-Cell Function

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Title: Uncovering Factors Related to Pancreatic Beta-Cell Function
Authors: Curran, Aoife M.
Ryan, Miriam F.
Drummond, Elaine
Gibney, Eileen R.
Gibney, Michael J.
Roche, Helen M.
Brennan, Lorraine
Permanent link: http://hdl.handle.net/10197/8306
Date: 18-Aug-2016
Abstract: 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.
Funding Details: Department of Agriculture, Food and the Marine
Enterprise Ireland
European Research Council
Science Foundation Ireland
Type of material: Journal Article
Publisher: Public Library of Science
Copyright (published version): 2016 the Authors
Keywords: Diabetes mellitus type 2;Pancreatic beta-cells
DOI: 10.1371/journal.pone.0161350
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Public Health, Physiotherapy and Sports Science Research Collection
Agriculture and Food Science Research Collection

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