Glomerulosclerosis in the Long-term Alloxan Diabetic Monkey

Gibbs, Gordon E.; Wilson, R. B.; Gifford, Houghton

doi:10.2337/diab.15.4.258

Cited by 38 publications

(11 citation statements)

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“…Although similar MM expansion has been identified in diabetic monkeys [Jonasson et al. 1984: Gibbs et al. 1966 and is confirmed by SEM and TEM in the current investigation, the endothe lial-mesangial layer has received relatively little attention in the monkey model.…”

Section: Discussionmentioning

confidence: 69%

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Ultrastructural Analyses of Acellular Glomerular Basement Membranes and Mesangial Matrix in a Spontaneously Diabetic Rhesus Monkey

Marion

Carlson²

1989

Cells Tissues Organs

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Renal changes similar to those considered diagnostic for diabetes in humans are infrequently observed in spontaneous noninsulin-dependent (NID) diabetic monkeys. In the current study, renal cortical tissue blocks are rendered acellular to demonstrate glomerular basement membrane (GBM) and mesangial matrix (MM) changes in a naturally occurring NID diabetic rhesus monkey (Macaca mulatta). Transmission electron micrographs of these specimens show axial MM accumulations with numerous striated collagen fibrils that frequently extend onto internal (endothelial) surfaces of peripheral GBM. The outer (epithelial) component, although compact, appears bilaminar due to folded external surfaces not coinciding with similar irregularities on internal surfaces. By scanning electron microscopy, external surfaces of sclerotic GBMs are extensively wrinkled and, following cryofracture, show congestion and expanded MM. Afenestrated meshwork of MM, which appears less dense and compact than epithelial BM, extends from axial regions onto GBM internal surfaces. The true thickness of randomly sampled peripheral GBM thickness (∼ 400 nm) is approximately double that of normal rhesus GBM. Diabetic GBMs exhibit ruthenium red positivity for surface polyanions with linear site densities not significantly different from normal. These observations indicate that sclerotic GBMs in diabetic rhesus monkeys closely resemble those seen in human endsfage diabetic glomerulopathy and suggest that this nonhuman primate may offer an excellent model for studies of chronic diabetic BM disease.

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Section: Discussionmentioning

confidence: 69%

“…Several morphological studies of diabetic rhesus monkey GBMs describe BM thickening and MM expan sion similar to classical changes in end-stage human dia betic kidney disease [Gibbs et al, 1966;Jonasson et al. 1984;Jones et al.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Analyses of Acellular Glomerular Basement Membranes and Mesangial Matrix in a Spontaneously Diabetic Rhesus Monkey

Marion

Carlson²

1989

Cells Tissues Organs

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“…Studies in diabetic rats, dogs and monkeys have shown that glomerular and/or retinal capillary membrane thickening undoubtedly develops after the induction of diabetes [60][61][62][63][64][65][66][67][68][69][70][71]. This includes the streptozotocin-hyperglycaemic rats studied by Mauer [71].…”

Section: Clinical Microangiopathy and Pathologic Changes In Animals Wmentioning

confidence: 99%

Relation of diabetic control to development of microvascular complications

Tchobroutsky

1978

Diabetologia

401

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Summary. This review seeks to supply the arguments which support or deny the relationship between the quality of control of blood glucose levels and the course of diabetic microangiopathy. The ideal study is impossible to do in man but most prospective studies suggest that the better the control the slower the rate of progression and severity of lesions. "Scientific" but indirect arguments from biochemical, enzymatic and functional studies have shown that insulin and/or blood glucose control reverse some early diabetic changes that are probably related to the late events. Recent studies suggest that observations on animals that have shown the beneficial effect of treatment are relevant to the problem of diabetic microvascular lesions in man. Heredity influences the development of diabetic microangiopathy in diabetics but retinal and/or glomerular lesions -which are definitely not pathognomonic for diabetes -do not appear in the absence of hyperglycaemia. Muscle capillary basement membrane thickening that seems not to be a specific abnormality was not observed by several investigators in recently diagnosed diabetics. Therefore most of the arguments that have been given to support the point of view that tight control is not justified may be rejected. The opinion of the author is that strict control of diabetes is worthwile in patients with long life expectancy and no psychological, social or cultural handicaps.

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“…Although the incidence of microvascular disease of patients with secondary diabetes has often not been as great as in those with idiopathic diabetes this can be attributed to the shorter survival of individuals with the primary pancreatic disease. Evidence of microvascular disease in kidney, retina or musclehas now been observed in chemically or hormonally induced diabetes of dogs, rats, and rhesus monkeys as well as in spontaneous diabetes of Chinese hamsters, KK mice and Celebes apes [59][60][61][62][63][64]. In the Celebes apes, in which the diabetes appears to be the result of infiltration of amyloid into the islets of Langerhans, the extent of muscle capillary basement membrane thickness has been correlated in an impressive manner to the degree of serum insulin decrease as well as to the serum glucose elevation [64].…”

Section: Metabolic Hypothesis Of Diabetic Microangiopathymentioning

confidence: 99%

Search for a biochemical basis of diabetic microangiopathy

1976

Diabetologia

191

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Summary. Diabetic microangiopathy, particularly as seen in the renal glomerulus, is characterized by morphological and biochemical alterations of the capillary basement membrane. Observations from a number of disciplines have indicated that the microvascular disease is not a separately inherited entity but a true consequence or "complication" of insulin deficiency. An evaluation of the biochemical events which could be responsible for the basement membrane lesions of diabetes indicates that the hyperglycemia or plasma somatotropin elevation of this disease alone, or in combination, may play an important role.

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Glomerulosclerosis in the Long-term Alloxan Diabetic Monkey

Cited by 38 publications

References 0 publications

Ultrastructural Analyses of Acellular Glomerular Basement Membranes and Mesangial Matrix in a Spontaneously Diabetic Rhesus Monkey

Ultrastructural Analyses of Acellular Glomerular Basement Membranes and Mesangial Matrix in a Spontaneously Diabetic Rhesus Monkey

Relation of diabetic control to development of microvascular complications

Search for a biochemical basis of diabetic microangiopathy

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