TY - JOUR
T1 - Arachidonic acid metabolism in isolated pancreatic islets. III. Effects of exogenous lipoxygenase products and inhibitors on insulin secretion
AU - Turk, John
AU - Colca, Jerry R.
AU - McDaniel, Michael L.
N1 - Funding Information:
Washington University Biomedical Research Support Grants Program (NIH BRSG SO7 RR053&9), the Pharmaceutical Manufacturer’s Association Foundation, the Juvenile Diabetes Foundation and the National Institutes of Health (AM 34388).T he excellent technical assistance of Richard Thoma, Deidre Buscetto and C. Joan Fink has been greatly appreciated as has the interest and advice of Dr. Jay McDonald, Dr. Paul Lacy an Dr. Philip Needleman. Special thanks are due to Jane Huth for the preparation of the manuscript. We are grateful to Dr. Aubrey Morrison and to Dr. William Sherman for providing accesst o the Hewlett-Packard 5985B mass spectometer within the Washington University Mass Spectrometry Resource Center which is supported by NIH grasrt RR 00954.
Funding Information:
This work was supportedin part by a grant to M.L.M. from the National Institutes of Health (AM 06181) and by grants to J.T. from the Washington University Diabetes Research and Training Center (NIADDK P60 AM20579), the
PY - 1985/3/27
Y1 - 1985/3/27
N2 - Isolated pancreatic islets from the rat have been demonstrated by stable isotope dilution-mass spectrometric methods to synthesize the 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE) in amounts of 1.7 to 2.8 ng per 103 islets. No detectable amounts of 5-HETE and only trace amounts of 15-HETE could be demonstrated by these methods. Nordihydroguaiaretic acid (NDGA) and BW755C have been demonstrated to inhibit islet 12-HETE synthesis and also to inhibit glucose-induced insulin secretion. Inhibition of insulin secretion and of 12-HETE synthesis exhibited similar dependence on the concentration of these compounds. Eicosa-5,8,11,14-tetrynoic acid (ETYA) also inhibited glucose-induced insulin secretion, as previously reported, at concentrations which inhibit islet 12-HETE synthesis. Exogenous 12-HETE partially reversed the suppression of glucose-induced insulin secretion by lipoxygenase inhibitors, but exogenous 12-hydroperoxyeicosatetraenoic acid (12-HPETE), 15-HPETE, 5-HPETE, 15-HETE, or 5-HETE did not reverse this suppression. These observations argue against the recently suggested hypothesis that islet synthesis of 5-HETE modulates insulin secretion. Suppression of glucose-induced insulin secretion by ETYA, BW755C and NDGA may be due to inhibition of the islet 12-lipoxygenase by these compounds. The possibility that other processes involved in glucose-induced insulin secretion are inhibited by ETYA, BW755C and NDGA cannot yet be excluded.
AB - Isolated pancreatic islets from the rat have been demonstrated by stable isotope dilution-mass spectrometric methods to synthesize the 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE) in amounts of 1.7 to 2.8 ng per 103 islets. No detectable amounts of 5-HETE and only trace amounts of 15-HETE could be demonstrated by these methods. Nordihydroguaiaretic acid (NDGA) and BW755C have been demonstrated to inhibit islet 12-HETE synthesis and also to inhibit glucose-induced insulin secretion. Inhibition of insulin secretion and of 12-HETE synthesis exhibited similar dependence on the concentration of these compounds. Eicosa-5,8,11,14-tetrynoic acid (ETYA) also inhibited glucose-induced insulin secretion, as previously reported, at concentrations which inhibit islet 12-HETE synthesis. Exogenous 12-HETE partially reversed the suppression of glucose-induced insulin secretion by lipoxygenase inhibitors, but exogenous 12-hydroperoxyeicosatetraenoic acid (12-HPETE), 15-HPETE, 5-HPETE, 15-HETE, or 5-HETE did not reverse this suppression. These observations argue against the recently suggested hypothesis that islet synthesis of 5-HETE modulates insulin secretion. Suppression of glucose-induced insulin secretion by ETYA, BW755C and NDGA may be due to inhibition of the islet 12-lipoxygenase by these compounds. The possibility that other processes involved in glucose-induced insulin secretion are inhibited by ETYA, BW755C and NDGA cannot yet be excluded.
KW - (Rat pancreatic islet)
KW - Arachidonate metabolism
KW - Hydroxyeicosanoic acid
KW - Insulin secretion
KW - Lipoxygenase
UR - http://www.scopus.com/inward/record.url?scp=0021907945&partnerID=8YFLogxK
U2 - 10.1016/0005-2760(85)90172-9
DO - 10.1016/0005-2760(85)90172-9
M3 - Article
C2 - 3919770
AN - SCOPUS:0021907945
VL - 834
SP - 23
EP - 36
JO - Biochimica et Biophysica Acta - Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta - Lipids and Lipid Metabolism
SN - 0005-2760
IS - 1
ER -