Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques.
Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.
Heffernan
S
S
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
James
V
V
Zilkens
R
R
Kirwan
P
P
Birrell
A
A
McLennan
S
S
Hennessy
A
A
Gillin
A
A
Horvath
J
J
Tiller
D
D
Yue
D
D
Turtle
J
J
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D005109:Extracellular Matrix / Q000648:ultrastructure*; D005920:Glomerular Mesangium / Q000473:pathology; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008854:Microscopy, Electron; D010215:Papio; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology*; D013710:Tendons / Q000473:pathology*; D014961:X-Ray Diffraction