Glucose-stimulated insulin secretion correlates with beta-cell lipolysis.
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.
Winzell
Maria Sörhede
MS
Department of Clinical Sciences, Medicine, Lund University, Biomedical Center, Lund, Sweden. maria.sorhede_winzell@med.lu.se
Ström
Kristoffer
K
Holm
Cecilia
C
Ahrén
Bo
B
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
D004791:Enzyme Inhibitors; D007328:Insulin; D007783:Lactones; D000077403:Orlistat; D008071:Lipoprotein Lipase; D005947:Glucose; D005990:Glycerol