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Endocrine Abstracts (2019) 65 OC1.6 | DOI: 10.1530/endoabs.65.OC1.6

Imperial College London, London, UK


Background: Both metabolic surgery and sodium glucose co-transporter (SGLT2) inhibitors have been demonstrated to improve insulin sensitivity and glucose clearance, but also increase glucagon secretion and cardiovascular health.

Aim: To examine the effect of metabolic surgery (Vertical Sleeve Gastrectomy; VSG) on SGLT2 expression in kidney cortex of lean mice.

Methods: In order to assess whether exogenous SGLT2 inhibition has the same euglycemic effects as bariatric surgery, 14 lean mice underwent VSG (n=8) or sham (n=6) surgery. Glucose (3 g/kg) tolerance tests with or without treatment with the SGLT2 inhibitor dapagliflozin were performed four weeks post operatively. Kidneys were harvested from fed mice and analysed using Quantitative real-time PCR (qRT-PCR) and immunofluorescence.

Results: Quantitative RT PCR and immunofluorescence analysis on mouse kidneys demonstrated a significant lowering of SGLT2 expression at both the protein (n=5, P=0.0007) and mRNA (n=7, P<0.0001) levels four weeks after VSG. VSG did not cause any weight loss when compared to sham operated mice (P=0.37, Mann-Whitney test). Nevertheless, VSG mice displayed significantly improved glucose tolerance (P<0.001) and insulin secretion (P<0.01), which was not further affected by dapagliflozin (10 mg/kg; P>0.05). In contrast, treatment of sham mice with dapagliflozin increased glucose tolerance, though to a lesser extent than VSG. Glucagon levels were elevated post VSG and post treatment with dapagliflozin in both VSG and sham groups (P<0.01). Glycosuria was observed in 2/5 VSG mice, yet not in controls.

Conclusions: Our previous results on the effects of Duodenal Jejunal Bypass in lean rats showed a significant lowering of SGLT2 expression, confirming that both gastric and intestinal surgery in lean animals causes a significant inhibition of SGLT2 in the kidney cortex. These findings point towards a physiologically-relevant gut-kidney axis. SGLT2 inhibition may thus be an important mechanism through which bariatric surgery improves glucose tolerance in man.

Volume 65

Society for Endocrinology BES 2019

Brighton, United Kingdom
11 Nov 2019 - 13 Nov 2019

Society for Endocrinology 

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