Abstract
Bariatric surgery improves both insulin sensitivity and secretion and can induce diabetes remission. However, the mechanisms and time courses of these changes, particularly the impact on β cell function, are difficult to monitor directly. In this study, we investigated the effect of Vertical Sleeve Gastrectomy (VSG) on β cell function in vivo by imaging Ca2+ dynamics in islets engrafted into the anterior eye chamber. Mirroring its clinical utility, VSG in mice results in significantly improved glucose tolerance, and enhanced insulin secretion. We reveal that these benefits are underpinned by augmented β cell function and coordinated activity across the islet. These effects involve changes in circulating GLP-1 levels which may act both directly and indirectly on the β cell, in the latter case through changes in body weight. Thus, bariatric surgery leads to time-dependent increases in β cell function and intra-islet connectivity which are likely to contribute to diabetes remission.
Highlights
Bariatric surgery improves both insulin sensitivity and secretion and can induce diabetes remission
We show that Vertical Sleeve Gastrectomy (VSG) increases β-cell Ca2+ dynamics within 8 weeks post-surgery when compared to pre-operative baseline and a sham-operated group
Mice were placed on a high-fat high-sucrose diet (HFHSD), at 8 weeks of age, 8 weeks before sham, or VSG surgery
Summary
Bariatric surgery improves both insulin sensitivity and secretion and can induce diabetes remission. A critical limitation in investigating β-cell function in living humans or preclinical models is that, in the absence of robust in vivo imaging technologies[22], function must be inferred from measurements of circulating insulin or C-peptide These approaches preclude any quantitation of changes over time, a detailed examination of function at the level of single β-cells, or the connections between them. In an effort to overcome these limitations, the present study aimed to directly and longitudinally observe the effect of vertical sleeve gastrectomy (VSG) on pancreatic β-cell function in mice, by transplanting “reporter” islets in the anterior chamber of the eye This approach was established by Berggren and colleagues[27] and has recently been developed by ourselves[26] to assess coordinated islet behaviour in vivo. These changes were associated with increased circulating GLP-1 levels, suggesting that enhanced incretin production contributes to postoperative improvements in β-cell performance
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