The intestinal microbiota has been demonstrated to influence host metabolism, and has been proposed to affect the development of obesity and type 2 diabetes (T2D), possibly through short-chain fatty acids (SCFAs) produced by fermentation of dietary fiber. There are some indications that SCFAs inhibit glucose-stimulated insulin secretion (GSIS) in rodents, but research on this subject is sparse. However, it has been reported that receptors for SCFAs, free fatty acid receptor 2 (FFAR2) and FFAR3 are expressed not only on gut endocrine cells secreting GLP-1 and PYY, but also on pancreatic islet cells. We hypothesized that SCFAs might influence the endocrine secretion from pancreatic islets similar to their effects on the enteroendocrine cells. We studied this using isolated perfused mouse pancreas which responded adequately to changes in glucose and to infusions of arginine. None of the SCFAs, acetate, propionate and butyrate, influenced glucagon secretion, whereas they had weak inhibitory effects on somatostatin and insulin secretion. Infusions of two specific agonists of FFAR2 and FFAR3, CFMB and Compound 4, respectively, did not influence the pancreatic secretion of insulin and glucagon, whereas both induced strong increases in the secretion of somatostatin. In conclusion, the small effects of acetate, propionate and butyrate we observed here may not be physiologically relevant, but the effects of CFMB and Compound 4 on somatostatin secretion suggest that it may be possible to manipulate pancreatic secretion pharmacologically with agonists of the FFAR2 and 3 receptors, a finding which deserves further investigation.

肠道菌群已被证明会影响宿主的新陈代谢，并已提出可能通过饮食纤维发酵产生的短链脂肪酸（SCFA）影响肥胖症和2型糖尿病（T2D）的发展。有迹象表明，SCFAs可抑制啮齿动物中葡萄糖刺激的胰岛素分泌（GSIS），但对此问题的研究很少。然而，据报道，SCFA的受体，游离脂肪酸受体2（FFAR2）和FFAR3不仅在分泌GLP-1和PYY的肠内分泌细胞上表达，而且在胰岛细胞上表达。我们假设SCFAs可能会影响胰岛的内分泌分泌，类似于它们对肠内分泌细胞的作用。我们使用分离的灌注小鼠胰腺进行了研究，该小鼠胰腺对葡萄糖的变化和精氨酸的注入有足够的反应。SCFA，乙酸根，丙酸根和丁酸根均不影响胰高血糖素的分泌，而它们对生长抑素和胰岛素分泌的抑制作用较弱。分别注入FFAR2和FFAR3，CFMB和化合物4的两种特定激动剂不会影响胰岛素和胰高血糖素的胰腺分泌，而两者均会诱导生长抑素的分泌大量增加。总之，我们在此处观察到的乙酸盐，丙酸盐和丁酸盐的微小作用可能在生理上不相关，但是CFMB和化合物4对生长抑素分泌的作用表明，可以用药理学上用FFAR2和3激动剂来操纵胰腺分泌受体，