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

Sep 4, 2017 | Magazine: International Journal of Obesity

Méndez-Giménez L (1,2), Becerril S (1,2), Camões SP (3), da Silva IV (3), Rodrigues C (3), Moncada R (2,4), Valentí V (2,5), Catalán V (1,2), Gómez-Ambrosi J (1,2), Miranda JP (3), Soveral G (3), Frühbeck G (1,2,6), Rodríguez A (1,2).

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.

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

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