The diabetic-prone BioBreeding Wistar rat (BB/DP) is an autoimmune model of insulindependent 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. © 2004 Wiley-Liss, Inc.
Key words: diabetes; glomerular basement membrane thickness; BB Wistar ratsThe BioBreeding Wistar rat (BB rat) is an autoimmune model of insulin-dependent diabetes mellitus (IDDM) discovered in 1974 in a colony of pathogen-free Wistar rats (Chappel and Chappel, 1983). Like human IDDM, the onset of clinical symptoms in diabetes-prone (BB/DP) BB rats appear during adolescence, generally between 60 and 120 days of age (Butler et al., 1983;Chappel and Chappel, 1983). These are characterized by rapid weight loss, polyuria, polydipsia, ketonuria, and finally death unless exogenous insulin is administered (Chappel and Chappel, 1983;Like and Rossini, 1984). The incidence of diabetes through 120 days of age is 60 -90% in most colonies and averaged 86% in a viral antibody-free NIH colony in Worcester, Massachusetts (Crisa et al., 1992). The diabetes exhibited by BB rats is not attributed to a single dominant or recessive gene, but the etiology seems to include a genetic component (Chappel and Chappel, 1983).
