320-OR: Bariatric Surgery Improves Ca2+ Dynamics across Pancreatic Islets In Vivo

Abstract

Background: Bariatric surgery improves both insulin sensitivity and secretion in T2D. However, the impact on insulin secretion is difficult to monitor directly, requiring correction for insulin sensitivity. The degree to which surgery impacts β-cell function versus mass, and the time course over which these changes occur, also remain unclear. Aim: To investigate the effect of bariatric surgery on β-cell function in vivo, we imaged Ca2+ dynamics prospectively at the cellular level in islets engrafted into the anterior eye chamber. Methods: Ins1Cre mice were crossed to animals that express the genetic calcium indicator GCaMP6f behind a Lox PSTOP<italic>LoxP cassette. Isolated islets were engrafted into male C57BL6 mice maintained for 12 weeks on high fat/high sucrose diet (HFD). At pre- (-1) and post-operative weeks 4, 8 and 12, Vertical Sleeve Gastrectomy (VSG) (n=7) and sham (n=6) groups were anaesthetized, and islets imaged in the eye using a Nikon microscope equipped with a spinning disc, 488 nm laser and 20x/1.0 water immersion objective. Islets were scored as positive for wave activity when these were recurrent, had a defined origin and covered >75 % of the image plane. Glucose (3g/kg) tolerance and insulin secretion were assessed in parallel. Results: The VSG group demonstrated substantial weight loss during the first 4 weeks post-operatively but regained pre-operative weight by week 12. Nonetheless, VSG mice displayed significantly improved glucose tolerance and insulin secretion (p<0.001) when compared to sham mice. VSG improved coordinated Ca2+ activity, with 100% of islets exhibiting enhanced wave readouts 8 weeks post surgery. Over the same time period islet wave activity dropped by 34% in the sham group, falling to zero discernible coordinated islet Ca2+ activity by week 12. Conclusions: By imaging islet function in the eye in vivo we demonstrate that bariatric surgery leads to a time-dependent increase in glucose-induced Ca2+ dynamics of individual islets, likely to underlie increased insulin secretion. Disclosure E. Akalestou: None. K. Suba: None. L. Lopez Noriega: None. P.L. Chabosseau: None. I. Leclerc: Consultant; Spouse/Partner; Sun Pharmaceutical Industries Ltd. Research Support; Spouse/Partner; Servier. V. Salem: None. G.A. Rutter: Consultant; Self; Sun Pharmaceutical Industries Ltd. Research Support; Self; Servier, Sun Pharmaceutical Industries Ltd. Funding UK Wellcome Trust (212625/Z/18/Z); Rosetrees Trust (M825); UK Medical Research Council (MR/R022259/1); Harry Keen Diabetes UK Fellowship (BDA 15/0005317); European Union