Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.
Int J Obes (Lond). 2017 Sep;41(9):1394-1402. doi: 10.1038/ijo.2017.135. Epub 2017 Jun 6.
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.
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.
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.
背景/目的：甘油是胰岛素敏感组织中脂质积累以及胰腺胰岛素分泌的关键代谢物。我们研究了水通道蛋白-7（AQP7），即β细胞中主要的甘油通道，以及水通道蛋白-12（AQP12），一种与胰腺损伤有关的水通道蛋白，在饮食诱导肥胖大鼠的袖状胃切除术后改善胰腺功能和脂肪变性中的作用。
受试者/方法：雄性 Wistar 肥胖大鼠（n=125）接受手术（假手术和袖状胃切除术）或饮食（与袖状胃切除动物所吃食物量相匹配的喂养）干预。通过实时 PCR、western blot 和免疫组织化学分析大鼠胰腺中 AQP 的组织分布和表达。在 RIN-m5F β细胞中，测定了 ghrelin 同工型和胰高血糖素样肽 1（GLP-1）对胰岛素分泌、三酰基甘油（TG）积累和 AQP 表达的影响。
袖状胃切除术减少了胰腺β细胞凋亡、脂肪变性和胰岛素分泌。减重手术后也发现了较低的 ghrelin 和较高的 GLP-1 浓度。酰化和去酰化 ghrelin 增加了 TG 含量，而 GLP-1 增加了 RIN-m5F β细胞中的胰岛素释放。袖状胃切除术与 AQP7 的上调以及大鼠胰腺中增加的 AQP12 水平的正常化相关。有趣的是，ghrelin 和 GLP-1 抑制了 RIN-m5F β细胞中 AQP7 和 AQP12 的表达。AQP7 蛋白与酰化 ghrelin 处理细胞中的细胞内脂质积累呈负相关，与 GLP-1 刺激的β细胞中的胰岛素释放呈负相关。
袖状胃切除术后β细胞中 AQP7 的上调部分通过增加用于 GLP-1 触发的胰岛素释放的细胞内甘油，而不是用于 ghrelin 诱导的 TG 生物合成，有助于改善胰腺脂肪变性和胰岛素分泌。
