Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic-prone BB Wistar rats.
The diabetic-prone BioBreeding Wistar rat (BB/DP) is an autoimmune model of insulin-dependent diabetes mellitus. Approximately 80-90% of the animals are hyperglycemic (BB/DP(h)) by 90-120 days of age while those that do not become diabetic in adolescence (BB/DP(n)) remain normoglycemic for life. Likewise, rats in the diabetes-resistant (BB/DR) strain are normoglycemic. Although renal morphological studies have been carried out in this model, ultrastructural observations of age- and diabetes-related extracellular matrix (ECM) changes, including glomerular basement membrane (GBM) morphometry, are not available. Moreover, possible renal changes in the relatively uncommon BB/DP(n) control animals have not been reported. The current electron microscopic study was carried out to investigate temporal changes in detergent-treated acellular ECM in BB/DP(h) rats at 2 weeks, 3 months, 6 months, and 1 year postonset of moderate hyperglycemia. Age-matched BB/DR and BB/DP(n) control animals were also examined. Our data demonstrate age- and diabetes-related alterations in mesangial matrix distributions and GBM widths and show for the first time significant increases in GBM thickening in both hyperglycemic (BB/DP(h)) and normoglycemic (BB/DP(n)) rats when compared to age-matched BB/DR controls. Surprisingly, the rate of increase is greatest in BB/DP(n) animals. Although the pathogenesis of diabetic basement membrane disease is not completely understood, GBM thickening is widely regarded as a morphological consequence of hyperglycemia. However, data in the current investigation show that ECM alterations, including significantly increased GBM thickness, may occur in genetically diabetic animals in the absence of hyperglycemia.
Carlson
Edward C
EC
Department of Anatomy and Cell Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202, USA. ecarlson@medicine.nodak.edu
Vari
Richard C
RC
Audette
Janice L
JL
Finke
Michelle A
MA
Ressler
Michael J
MJ
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011913:Rats, Inbred BB; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose