Nonparenchymal cells in chronically hyperinsulinemic liver acini of diabetic rats, with special regard to hepatic stellate cells.
OBJECTIVE
An increase in proliferative activity and other distinct hepatocellular alterations--resembling preneoplastic foci and progressing to hepatocellular tumors--have been shown to develop in liver acini draining the blood from islets of Langerhans, transplanted through the portal vein into the liver of streptozotocin-diabetic rats.


METHODS
Altered and unaltered liver acini were investigated for possible changes in hepatic stellate cells 4-76 days after islet transplantation.


RESULTS
Corresponding to a significant increase in the hepatocellular volume, the volume density of total nonparenchymal cells was significantly reduced in altered compared to unaltered liver acini. With regard to the total nonparenchymal cell volume, the hepatic stellate cell fraction was not different, whereas the fraction of Kupffer cells was significantly reduced and the fraction of sinusoidal endothelial cells was significantly increased in altered compared to unaltered liver acini, respectively. The volume density as well as the single volume of the hepatic stellate cell mitochondria increased significantly in altered compared to unaltered liver acini. Hepatic stellate cell lipid droplets did not show significant differences between altered and unaltered liver acini. In situ hybridization for hepatocyte growth factor mRNA showed no differences in intensity of the specific signals in hepatic stellate cells of altered versus unaltered liver acini. The transplanted islets were negative for hepatic growth factor mRNA.


CONCLUSIONS
The results suggest that hepatic growth factor production by hepatic stellate cells or by islet cells is not relevant to hepatocellular proliferative activity in altered liver acini.
Evert
M
M
Department of Pathology, University of Bonn, Germany.
Dombrowski
F
F
Schirmacher
P
P
Pfeifer
U
U
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006946:Hyperinsulinism / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D016381:Islets of Langerhans Transplantation; D016014:Linear Models; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew
D017228:Hepatocyte Growth Factor