Delta6-, Stearoyl CoA-, and Delta5-desaturase enzymes are expressed in beta-cells and are altered by increases in exogenous PUFA concentrations

Biochim Biophys Acta. 2002 Jan 30;1580(1):40-56. doi: 10.1016/s1388-1981(01)00189-5.

Abstract

In the evolution of Type II diabetes, an initial period of hyper-fatty acidemia leads to an insulin secretory defect which triggers overt hyperglycemia and frank diabetes. The mechanism by which elevated free fatty acids contribute to beta-cell dysfunction, however, is not clearly understood. We recently reported that arachidonic acid (20:4) or linoleic acid (18:2) supplementations result in increases in abundances of long chain polyunsaturated fatty acids in INS-1 beta-cell membrane lipids, suggesting that beta-cells express desaturases that catalyze generation of unsaturated fatty acids. As expression of desaturases by beta-cells has not yet been addressed, we initiated studies to examine this issue using INS-1 beta-cells and find that they express messages for the Delta6-, stearoyl CoA-, and Delta5-desaturase. Supplementation of the INS-1 beta-cells with arachidonic acid leads to decreased expression of all three desaturases, presumably in response to the decreased need for endogenous generation of unsaturated fatty acids. In contrast, linoleic acid supplementation promoted minimal changes in the three desaturases. These findings demonstrate for the first time that beta-cells express regulatable desaturases. Additionally, reverse transcriptase-polymerase chain reaction analyses reveal expression of the desaturases in native pancreatic islets. It might be speculated that long-term elevations in fatty acids can also adversely influence desaturase activity in beta-cells and affect PUFA composition in beta-cell membranes contributing to beta-cell membrane structural abnormalities and altered secretory function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acid / pharmacology
  • Dose-Response Relationship, Drug
  • Fatty Acid Desaturases / biosynthesis
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism*
  • Fatty Acids, Unsaturated / pharmacology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / enzymology
  • Linoleic Acid / pharmacology
  • Linoleoyl-CoA Desaturase
  • Mass Spectrometry
  • Phosphatidylethanolamines / metabolism
  • Phosphorylcholine / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stearoyl-CoA Desaturase / biosynthesis
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism
  • Tumor Cells, Cultured

Substances

  • Fatty Acids, Unsaturated
  • Phosphatidylethanolamines
  • RNA, Messenger
  • Phosphorylcholine
  • glycerophosphoethanolamine
  • Arachidonic Acid
  • Linoleic Acid
  • Fatty Acid Desaturases
  • Stearoyl-CoA Desaturase
  • Linoleoyl-CoA Desaturase
  • delta-5 fatty acid desaturase