Insulin binding and degradation by rat liver Kupffer and endothelial cells.
The liver is the major site of insulin metabolism. Previous studies have suggested that hepatocytes were chiefly responsible for this activity, while contributions of Kupffer and other nonparenchymal liver cells remained controversial. In this study, we compared 125I-insulin binding and degradation by rat hepatocytes with insulin binding and degradation by sinusoidal Kupffer and endothelial cells. Kupffer cells were separated from endothelial cells by centrifugal elutriation. Hepatocytes had approximately 3.5 times more insulin binding sites than Kupffer cells and approximately eight times more binding sites than endothelial cells. In addition, wheat germ agglutinin (WGA)-purified solubilized receptors from all three cell types bound insulin in proportions similar to whole cells. Moreover, all three cell types were shown with a ribonuclease (RNase) protection assay to express insulin receptor mRNA. Hepatocytes degraded approximately four times more insulin than Kupffer cells, while endothelial cells degraded only negligible amounts of insulin. Based on morphometric data available in the literature, we estimated that nonparenchymal cells could account for approximately 10% to 15% of hepatic insulin degradation. We concluded that rat hepatocytes, Kupffer cells, and endothelial cells all have specific insulin receptors, and that nonparenchymal cells play a small but significant role in insulin degradation.
Kolaczynski
J W
JW
Division of Endocrinology and Metabolism, Temple University School of Medicine, Philadelphia, PA.
Carter
R
R
Soprano
K J
KJ
Moscicki
R
R
Boden
G
G
D000818:Animals; D004727:Endothelium / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012260:Ribonucleases; D014909:Wheat Germ Agglutinins
D007328:Insulin; D012333:RNA, Messenger; D014909:Wheat Germ Agglutinins; D011972:Receptor, Insulin; D012260:Ribonucleases