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. 2017 Sep;41(9):1394-1402.
doi: 10.1038/ijo.2017.135. Epub 2017 Jun 6.

Role of aquaporin-7 in ghrelin- and GLP-1-induced improvement of pancreatic β-cell function after sleeve gastrectomy in obese rats

L Méndez-Giménez  1   2 , S Becerril  1   2 , S P Camões  3 , I V da Silva  3 , C Rodrigues  3 , R Moncada  2   4 , V Valentí  2   5 , V Catalán  1   2 , J Gómez-Ambrosi  1   2 , J P Miranda  3 , G Soveral  3 , G Frühbeck  1   2   6 , A Rodríguez  1   2
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Role of aquaporin-7 in ghrelin- and GLP-1-induced improvement of pancreatic β-cell function after sleeve gastrectomy in obese rats

L Méndez-Giménez et al. Int J Obes (Lond). 2017 Sep.

Abstract

Background/objectives: Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues as well as for pancreatic insulin secretion. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in β-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats.

Subjects/methods: Male Wistar obese rats (n=125) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by sleeve-gastrectomized animals) interventions. The tissue distribution and expression of AQPs in the rat pancreas were analyzed by real-time PCR, western blotting and immunohistochemistry. The effect of ghrelin isoforms and glucagon-like peptide 1 (GLP-1) on insulin secretion, triacylglycerol (TG) accumulation and AQP expression was determined in vitro in RIN-m5F β-cells.

Results: Sleeve gastrectomy reduced pancreatic β-cell apoptosis, steatosis and insulin secretion. Lower ghrelin and higher GLP-1 concentrations were also found after bariatric surgery. Acylated and desacyl ghrelin increased TG content, whereas GLP-1 increased insulin release in RIN-m5F β-cells. Sleeve gastrectomy was associated with an upregulation of AQP7 together with a normalization of the increased AQP12 levels in the rat pancreas. Interestingly, ghrelin and GLP-1 repressed AQP7 and AQP12 expression in RIN-m5F β-cells. AQP7 protein was negatively correlated with intracellular lipid accumulation in acylated ghrelin-treated cells and with insulin release in GLP-1-stimulated β-cells.

Conclusions: AQP7 upregulation in β-cells after sleeve gastrectomy contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1 rather than for ghrelin-induced TG biosynthesis.

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