MacDonald Michael J, Dobrzyn Agnieszka, Ntambi James, Stoker Scott W
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Room 3459 Medical Science Center, 1300 University Avenue, Madison, WI 53706, USA.
Arch Biochem Biophys. 2008 Feb 15;470(2):153-62. doi: 10.1016/j.abb.2007.11.017. Epub 2007 Dec 3.
Pancreatic beta cell mitochondria convert insulin secretagogues into products that support insulin exocytosis. We explored the idea that lipids are some of these products formed from acyl group transfer out of mitochondria to the cytosol, the site of lipid synthesis. There are two isoforms of acetyl-CoA carboxylase, the enzyme that forms malonyl-CoA from which C(2) units for lipid synthesis are formed. We found that ACC1, the isoform seen in lipogenic tissues, is the only isoform present in human and rat pancreatic islets and INS-1 832/13 cells. Inhibitors of ACC and fatty acid synthase inhibited insulin release in islets and INS-1 cells. Carbon from glucose and pyruvate were rapidly incorporated into many lipid classes in INS-1 cells. Glucose and other insulin secretagogues acutely increased many lipids with C14-C24 chains including individual cholesterol esters, phospholipids and fatty acids. Many phosphatidylcholines and phosphatidylserines were increased and many phosphatidylinositols and several phosphatidylethanolamines were decreased. The results suggest that lipid remodeling and rapid lipogenesis from secretagogue carbon support insulin secretion.
胰腺β细胞线粒体将胰岛素促分泌剂转化为支持胰岛素胞吐作用的产物。我们探讨了脂质是由线粒体酰基转移至脂质合成部位胞质溶胶所形成的部分此类产物这一观点。乙酰辅酶A羧化酶有两种同工型，该酶可形成丙二酰辅酶A，脂质合成的C(2)单位由此形成。我们发现，在脂肪生成组织中可见的同工型ACC1是人和大鼠胰岛及INS-1 832/13细胞中唯一存在的同工型。ACC和脂肪酸合酶的抑制剂可抑制胰岛和INS-1细胞中的胰岛素释放。葡萄糖和丙酮酸中的碳迅速掺入INS-1细胞中的多种脂质类别。葡萄糖和其他胰岛素促分泌剂可急性增加许多具有C14 - C24链的脂质，包括个别胆固醇酯、磷脂和脂肪酸。许多磷脂酰胆碱和磷脂酰丝氨酸增加，许多磷脂酰肌醇和几种磷脂酰乙醇胺减少。结果表明，促分泌剂碳源的脂质重塑和快速脂肪生成支持胰岛素分泌。
