title: Glucose-stimulated insulin secretion correlates with beta-cell lipolysis.
abstract: OBJECTIVE
  Lipids are needed for optimal glucose-stimulated insulin secretion (GSIS), and long-chain acyl-CoA (LC-CoA) has been suggested as one candidate molecule active as a lipidic coupling factor. LC-CoAs may be available to the beta-cell via uptake of circulating free fatty acids or from hydrolysis of intracellularly stored triglycerides. Inhibition of lipolysis in rat islets using a non-specific lipase inhibitor (orlistat) resulted in blunted GSIS. The aim of this study was to investigate the relationship between GSIS and lipolysis in clonal beta-cells and in mouse islets.
  
  
  RESULTS
  INS-1 cells, cultured overnight at 3.3 mM or 11.1 mM glucose, or freshly isolated islets were incubated with 3.3 mM or 16.7 mM glucose for 1 h. Medium samples were collected and analyzed for insulin and glycerol. Triglycerides were measured in both INS-1 cells and islets. There was a dose-dependent glucose-stimulated lipolysis in INS-1 cells, which strongly correlated with insulin secretion (r=0.85, P<0.0001). The same phenomenon was observed in mouse islets (r=0.9, P=0.013). Low levels of triglycerides, which were observed in INS-1 cells pre-cultured at 3.3 mM glucose, were associated with reduced GSIS.
  
  
  CONCLUSIONS
  This study suggests that lipids obtained from lipolysis of intracellular triglycerides are involved in GSIS.
authors.affiliation: Department of Clinical Sciences, Medicine, Lund University, Biomedical Center, Lund, Sweden. maria.sorhede_winzell@med.lu.se
authors.forename: Maria Sörhede
authors.initials: MS
authors.lastname: Winzell
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Ström
authors.forename: Cecilia
authors.initials: C
authors.lastname: Holm
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology; D008066:Lipolysis / Q000502:physiology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077403:Orlistat
chemical_list: D004791:Enzyme Inhibitors; D007328:Insulin; D007783:Lactones; D000077403:Orlistat; D008071:Lipoprotein Lipase; D005947:Glucose; D005990:Glycerol