Abstract:
UNASSIGNED: Studies suggest that short chain fatty acids (SCFAs), which are primarily produced from fermentation of fiber, regulate insulin secretion through free fatty acid receptors 2 and 3 (FFA2 and FFA3). As these are G-protein coupled receptors (GPCRs), they have potential therapeutic value as targets for treating type 2 diabetes (T2D). The exact mechanism by which these receptors regulate insulin secretion and other aspects of pancreatic β cell function is unclear. It has been reported that glucose-dependent release of acetate from pancreatic β cells negatively regulates glucose stimulated insulin secretion. While these data raise the possibility of acetate\'s potential autocrine action on these receptors, these findings have not been independently confirmed, and multiple concerns exist with this observation, particularly the lack of specificity and precision of the acetate detection methodology used.
UNASSIGNED: Using Min6 cells and mouse islets, we assessed acetate and pyruvate production and secretion in response to different glucose concentrations, via liquid chromatography mass spectrometry.
UNASSIGNED: Using Min6 cells and mouse islets, we showed that both intracellular pyruvate and acetate increased with high glucose conditions; however, intracellular acetate level increased only slightly and exclusively in Min6 cells but not in the islets. Further, extracellular acetate levels were not affected by the concentration of glucose in the incubation medium of either Min6 cells or islets.
UNASSIGNED: Our findings do not substantiate the glucose-dependent release of acetate from pancreatic β cells, and therefore, invalidate the possibility of an autocrine inhibitory effect on glucose stimulated insulin secretion.
摘要:
■研究表明,短链脂肪酸(SCFA),主要由纤维发酵产生,通过游离脂肪酸受体2和3(FFA2和FFA3)调节胰岛素分泌。由于这些是G蛋白偶联受体(GPCRs),它们作为治疗2型糖尿病(T2D)的靶点具有潜在的治疗价值.这些受体调节胰岛素分泌和胰腺β细胞功能的其他方面的确切机制尚不清楚。已经报道,从胰腺β细胞的乙酸盐的葡萄糖依赖性释放负调节葡萄糖刺激的胰岛素分泌。虽然这些数据提高了乙酸盐对这些受体的潜在自分泌作用的可能性,这些发现尚未得到独立证实,这种观察存在多种担忧,特别是使用的乙酸盐检测方法缺乏特异性和精确性。
■使用Min6细胞和小鼠胰岛,我们评估了乙酸盐和丙酮酸盐的产生和分泌对不同葡萄糖浓度的反应,通过液相色谱质谱。
■使用Min6细胞和小鼠胰岛,我们表明,细胞内丙酮酸和乙酸盐都在高葡萄糖条件下增加;然而,Min6细胞中的细胞内乙酸盐水平仅略有增加,仅在胰岛中增加。Further,细胞外乙酸盐水平不受Min6细胞或胰岛孵育培养基中葡萄糖浓度的影响。
■我们的发现没有证实胰腺β细胞葡萄糖依赖性释放乙酸,因此,使自分泌抑制作用对葡萄糖刺激的胰岛素分泌的可能性无效。