Inhibitory effects of Cimicifuga heracleifolia extract on glutamate formation and glutamate dehydrogenase activity in cultured islets.
Hyperinsulinism-hyperammonemia syndrome is due either to hyperactivity of GDH or impaired inhibition of GDH by GTP. We have investigated the effect of Cimicifuga heracleifolia extract on the activities of glutamate dehydrogenase (GDH) in cultured rat islets. When the extract was present in the culture medium for 24 h prior to cell harvest, the Vmax of GDH was decreased by 45% with no significant change in Km. In addition, the concentration of alpha-ketoglutarate increased by approximately 39%, and glutamate decreased by 48%. Perfusion of islets with C. heracleifolia extract reduced insulin release by up to 47%. Although the relation between GDH activity and insulin release remains to be clarified, our results suggest that C. heracleifolia extract regulates insulin release by altering GDH activity in primary cultured islets and that this natural compound may be used to modulate GDH activity in patients with hyperinsulinism-hyperammonemia syndrome.
Lee
Kwan Ho
KH
Pulmonary Division of Internal Medicine, Yeungnam University School of Medicine, Daegu, Korea.
Lee
Woo-Je
WJ
Yang
Seong-Ju
SJ
Huh
Jae-Wan
JW
Choi
Jene
J
Hong
Hea-Nam
HN
Hwang
Onyou
O
Cho
Sung-Woo
SW
D000818:Animals; D031885:Cimicifuga / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity; D005969:Glutamate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D007656:Ketoglutaric Acids / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010936:Plant Extracts / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007328:Insulin; D007656:Ketoglutaric Acids; D010936:Plant Extracts; D018698:Glutamic Acid; D005969:Glutamate Dehydrogenase