The role of rapid lipogenesis in insulin secretion: Insulin secretagogues acutely alter lipid composition of INS-1 832/13 cells

• Published in: Archives of biochemistry and biophysics Vol. 470; no. 2; pp. 153 - 162
• Main Authors: MacDonald, Michael J., Dobrzyn, Agnieszka, Ntambi, James, Stoker, Scott W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2008
• Subjects: Acetyl-CoA carboxylase; Acetyl-CoA Carboxylase - metabolism; Anaplerosis; Animals; Cell Line; Cholesterol esters; Fatty acid synthase; Glucose - metabolism; INS-1 832/13 cells; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - physiology; Lipid Metabolism - physiology; Lipid remodeling; Lipogenesis; Lipogenesis - physiology; Pancreatic islets; Phospholipids; Rats; Cholesterol esters; Acetyl-CoA carboxylase; Lipid remodeling; Pancreatic islets; Fatty acid synthase; Phospholipids; INS-1 832/13 cells; Lipogenesis; Anaplerosis
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2007.11.017

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 C 14–C 24 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.