Blood glucose control and glomerular capillary basement membrane thickening in experimental diabetes.

Fox, Charles; Darby, S C; Ireland, J. T.; Sönksen, P. H.

doi:10.1136/bmj.2.6087.605

Cited by 75 publications

(23 citation statements)

References 5 publications

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“…Islet cell transplantation into diabetic rats which results in normalization of carbohydrate metabolism, also causes reversal of established renal lesions [20]. Vigorous insulin therapy has been shown to prevent development of mesangial and glomerular basement membrane thickening in rats with either experimental [21][22][23][24] or spontaneous [18] diabetes. Moreover, it has been reported that STZ does not possess any significant nephrotoxic potential [25].…”

Section: Discussionmentioning

confidence: 99%

Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats

Shinde

Goyal

2003

J Cellular Molecular Medi

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Earlier studies from our laboratory have indicated insulin sensitizing action of chromium picolinate as the mechanism of its anti‐diabetic activity in experimental models of type I and type II diabetes. In the present investigation, we have evaluated the effects of chronic administration of chromium picolinate on the functional and histological alterations of streptozotocin (STZ)‐induced diabetes in rats. Type I diabetes was induced by intravenous injection of STZ (40 mg/kg) in adult rats, whereas, type II diabetes was induced by intraperitoneal injection of STZ (90 mg/kg) in 2‐day old rat pups which in adulthood develop abnormalities resembling type II diabetes. Chromium picolinate was administered at 8 μg/ml in drinking water for 6 weeks and was found to improve glucose tolerance and increase insulin sensitivity of STZ‐diabetic rats. This treatment decrease elevated serum creatinine and urea levels as well as elevated serum levels of hepatic enzymes of both groups of diabetic rats. Histopathological studies of kidney and liver show decrease in the intensity and incidence of vacuolations, cellular infiltration and hypertrophy of STZ and nSTZ (neonatal STZ) diabetic rats. Chronic treatment with chromium picolinate however, did not alter the normal function or morphology of control rats. Chronic chromium picolinate at the therapeutic doses that improved glucose tolerance, was observed to have no hepatotoxic or nephrotoxic potential. It was rather found to improve renal and hepatic function and to reduce abnormalities associated with STZ‐diabetes. Chromium picolinate could play an important role in the long term management of diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats

Shinde

Goyal

2003

J Cellular Molecular Medi

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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%

“…In chronic hyperglycaemic eels the thickness of the basement membrane of the fete capillaries is increased [72]. Whatever the significance [73] of such a lesion "generally held to be the sine qua non of diabetic nephropathy" (10) it should be recalled that in animals with experimentally-induced diabetes, the reduction of hyperglycaemia by conventional or "ideal" treatments of the disease prevents, reduces, reverses or minimizes the formation of diabetic-like lesions in the kidney including capillary membrane thickening [59,66,[68][69][70][74][75][76][77][78][79][80].…”

Section: Clinical Microangiopathy and Pathologic Changes In Animals Wmentioning

confidence: 99%

Relation of diabetic control to development of microvascular complications

Tchobroutsky

1978

Diabetologia

399

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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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“…The mechanisms and prevention of the long-standing complications of microangiopathy remain unclear. Recent studies in the diabetic dog and human confirm a long-standing clinical suspicion that optimal control of plasma glucose levels will prevent microangiopathy (10)(11)(12). These findings and recent insight into the process of nonenzymatic glycosylation suggest that hyperglycemia per se may be ofdirect importance in the pathogenesis of diabetic complications.…”

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confidence: 97%

Micropinocytic ingestion of glycosylated albumin by isolated microvessels: possible role in pathogenesis of diabetic microangiopathy.

Williams¹,

Devenny²,

Bitensky³

1981

Proc. Natl. Acad. Sci. U.S.A.

128

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Microvessels isolated from rat epididymal fat exhibit differential vesicular ingestion rates for unmodified and nonenzymatically glycosylated rat albumin. While unmodified rat albumin is excluded from ingestion by endothelial micropinocytic vesicles, glycosylated albumin is avidly taken up by endocytosis. Interaction ofalbumin and glycosylated albumin with endothelium was studied with a double-label fluorescence assay of micropinocytosis. When glycosylated albumin was present at a concentration of 6% with respect to total albumin (the level found in "non diabetic" serum), only glycosylated albumin was ingested. At higher concentrations of glycosylated albumin (those found in diabetic serum), both albumin and glycosylated albumin are ingested. Glycosylation of endothelial membrane components results in stimulated ingestion of glycosylated albumin, persistent exclusion of unmodified albumin, and unaltered micropinocytic ingestion of native ferritin. These results indicate that nonenzymatic glycosylation of serum albumin may result in rapid vesicle-mediated extravasation of albumin. Chronic microvascular leakage of glycosylated albumin could contribute to the pathogenesis of diabetic microangiopathy.Molecular "languages" shape the complex interactions that support life processes. Unique symbols, fidelity of transcription, and rules of grammar are features of the genetic code (1). Specificity ofrecognition and informational content are also apparent in the interactions ofhormones with receptors (2), antigens with antibodies (3), and substrates with enzymes (4). In each ofthese examples, accurate recognition of a unique molecular conformation is crucial for the underlying process. Moreover, lapses in the fidelity of recognition can produce catastrophic results for the systems involved.Endothelial micropinocytosis provides a bidirectional large pore conduit for the transendothelial transport of macromolecules. Another form of molecular language is manifest in the interactions of such molecules with the caveolar (plasmalemmal vesicle) membrane components of endothelial cells. The use of this molecular language in the process ofrecognition-dependent endocytosis provides a discrimination function for transendothelial transport. There results a striking heterogeneity in the rates oftransendothelial vesicular transport ofa variety ofserum components (5-8).The reasons for these differences must be sought in specific interactions between each of the components and putative recognition sites in lumenal endothelial membranes. Such sites are situated within or adjacent to the stomata of caveolae and actively regulate the process of adsorptive endocytosis. Serum albumin appears virtually excluded from ingestion by micropinocytic vesicles (5). This exclusion cannot be attributed solely to the molecular dimensions or the net charge of albumin. Ferritin, which is larger and of similar net charge, is readily ingested by endothelial vesicles. The fine molecular details that govern these recognition processes, and thus modula...

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Blood glucose control and glomerular capillary basement membrane thickening in experimental diabetes.

Cited by 75 publications

References 5 publications

Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats

Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats

Relation of diabetic control to development of microvascular complications

Micropinocytic ingestion of glycosylated albumin by isolated microvessels: possible role in pathogenesis of diabetic microangiopathy.

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