Exp Mol Med.  2010 Jun;42(6):456-464. 10.3858/emm.2010.42.6.047.

Role of phospholipase D1 in glucose-induced insulin secretion in pancreatic beta cells

• Ma WN
• Park SY
• Han JS

• KMID: 1078361
• DOI: http://doi.org/10.3858/emm.2010.42.6.047

Abstract

As glucose is known to induce insulin secretion in pancreatic beta cells, this study investigated the role of a phospholipase D (PLD)-related signaling pathway in insulin secretion caused by high glucose in the pancreatic beta-cell line MIN6N8. It was found that the PLD activity and PLD1 expression were both increased by high glucose (33.3 mM) treatment. The dominant negative PLD1 inhibited glucose-induced Beta2 expression, and glucose-induced insulin secretion was blocked by treatment with 1-butanol or PLD1-siRNA. These results suggest that high glucose increased insulin secretion through a PLD1-related pathway. High glucose induced the binding of Arf6 to PLD1. Pretreatment with brefeldin A (BFA), an Arf inhibitor, decreased the PLD activity as well as the insulin secretion. Furthermore, BFA blocked the glucose-induced mTOR and p70S6K activation, while mTOR inhibition with rapamycin attenuated the glucose induced Beta2 expression and insulin secretion. Thus, when taken together, PLD1 would appear to be an important regulator of glucose-induced insulin secretion through an Arf6/PLD1/mTOR/p70S6K/Beta2 pathway in MIN6N8 cells.

Keyword

ADP-ribosylation factor 6; insulin; insulin-secreting cells; mTOR protein; phospholipase D1

MeSH Terms

ADP-Ribosylation Factors/metabolism/physiology
Animals
Basic Helix-Loop-Helix Transcription Factors/metabolism/physiology
Cells, Cultured
Gene Expression Regulation, Enzymologic/drug effects
Glucose/*pharmacology
Insulin/*secretion
Insulin-Secreting Cells/*drug effects/enzymology/metabolism/secretion
Intracellular Signaling Peptides and Proteins/metabolism/physiology
Mice
Models, Biological
Oligodeoxyribonucleotides, Antisense/pharmacology
Phospholipase D/antagonists & inhibitors/genetics/metabolism/*physiology
Protein-Serine-Threonine Kinases/metabolism/physiology
Ribosomal Protein S6 Kinases, 70-kDa/metabolism/physiology
Signal Transduction/drug effects/genetics