Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes.
OBJECTIVE
Diabetes mellitus is associated with extensive vascular pathology, yet little is known about its long-term effects on liver sinusoidal endothelial cells (LSECs). Potential diabetic changes in LSECs are important because of the role played by fenestrations in the LSECs in hepatic disposition of lipoproteins.


METHODS
Surgical liver biopsies for electron microscopy and immunohistochemistry were obtained from baboons with long-standing streptozotocin-induced, insulin-treated diabetes mellitus and compared with those from age-matched control animals.


RESULTS
There was an increase in the thickness of LSECs (170 +/- 17 vs 123 +/- 10 nm, p < 0.01). Fenestrations in LSECs, as determined by overall porosity, were markedly reduced (1.4 +/- 0.1% vs 2.6 +/- 0.2%, p < 0.01). Increased numbers of stellate cells were seen on electron microscopy, and this finding was corroborated by increased smooth muscle actin expression. Diabetes mellitus was also associated with increased endothelial production of von Willebrand factor and caveolin-1.


CONCLUSIONS
Diabetes mellitus in the non-human primate is associated with marked changes in LSECs, including a reduction in fenestrations. Such changes provide an additional and novel mechanism for impaired hepatic lipoprotein clearance and post-prandial hyperlipidaemia in diabetes mellitus.
Jamieson
H A
HA
Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW, Australia. hjamieson@med.usyd.edu.au.|ANZAC Research Institute, Concord RG Hospital and University of Sydney, Concord, NSW, 2139, Australia. hjamieson@med.usyd.edu.au.|Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. hjamieson@med.usyd.edu.au.
Cogger
V C
VC
Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW, Australia.|ANZAC Research Institute, Concord RG Hospital and University of Sydney, Concord, NSW, 2139, Australia.
Twigg
S M
SM
Department of Endocrinology, Royal Prince Alfred Hospital and University of Sydney, Camperdown, NSW, Australia.
McLennan
S V
SV
Department of Endocrinology, Royal Prince Alfred Hospital and University of Sydney, Camperdown, NSW, Australia.
Warren
A
A
Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW, Australia.|ANZAC Research Institute, Concord RG Hospital and University of Sydney, Concord, NSW, 2139, Australia.
Cheluvappa
R
R
Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW, Australia.|ANZAC Research Institute, Concord RG Hospital and University of Sydney, Concord, NSW, 2139, Australia.
Hilmer
S N
SN
Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW, Australia.|Department of Aged Care, Royal North Shore Hospital, St Leonards, NSW, Australia.|Department of Clinical Pharmacology, Royal North Shore Hospital, St Leonards, NSW, Australia.
Fraser
R
R
Department of Pathology, Christchurch School of Medicine, University of Otago, Christchurch, New Zealand.
de Cabo
R
R
Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Le Couteur
D G
DG
Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW, Australia.|ANZAC Research Institute, Concord RG Hospital and University of Sydney, Concord, NSW, 2139, Australia.
D000818:Animals; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology* / Q000648:ultrastructure; D006442:Glycated Hemoglobin / Q000032:analysis; D008055:Lipids / Q000097:blood; D008099:Liver / Q000473:pathology* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D010215:Papio
D001786:Blood Glucose; D001798:Blood Proteins; D006442:Glycated Hemoglobin; D008055:Lipids