The role of rapid lipogenesis in insulin secretion: Insulin secretagogues acutely alter lipid composition of INS-1 832/13 cells.
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.
MacDonald
Michael J
MJ
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Room 3459 Medical Science Center, 1300 University Avenue, Madison, WI 53706, USA. mjmacdon@wisc.edu
Dobrzyn
Agnieszka
A
Ntambi
James
J
Stoker
Scott W
SW
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D050155:Lipogenesis / Q000502:physiology*; D051381:Rats
D007328:Insulin; D000103:Acetyl-CoA Carboxylase; D005947:Glucose