Renal Sorbitol, myo-Inositol and Glycerophosphorylcholine in Streptozotocin-Diabetic Rats

Schmolke, Michael; Schleicher, Erwin; Guder, W. G.

doi:10.1515/cclm.1992.30.10.607

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…This is confirmed by the finding of the lowest sorbitol concentrations in this nephron segment even under diabetic conditions (10 Degradation of filtered proteins in the proximal tubule is largely facilitated by lysosomal proteases. Guder referred to the observation that the proximal tubule and the liver contain sufficient sorbitol dehydrogenase to convert extracellular sorbitol to fructose.…”

Section: Tubular Functionsupporting

confidence: 72%

Symposium Communications

1992

Clinical Chemistry and Laboratory Medicine

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Recent scientific developments have greatly increased our knowledge of the pathomechanisms of renal diseases. In parallel new analytical techniques have been described for the exclusion, detection and differentiation of glomerular and tubular dysfunctions.The organizers of this symposium therefore invited colleagues active in Renal Biochemistry and Physiology, Clinical Chemistry and Clinical Nephrology to exchange their present knowledge and discuss the possible diagnostic impact of recent developments. The meeting was held as a satellite to the 5th European Congress of Clinical Chemistry, Krakow, Poland. It was generously sponsored by Boehringer Mannheim, Germany.Most contributions are given as original papers in the present issue. Therefore this report concentrates on the discussions and conclusions of the meeting. The readers are referred to the original literature for detailed information. Glomerular Filtration H. J.Schurek reported on the present understanding of the mechanisms which determine glomerular permeability (1). According to present knowledge, glomerular filtration of proteins is limited by a size-selective and a charge-selective barrier. Under normal conditions, albumin permeability is lower than expected from the size of the molecule, indicating that negative charges prevent albumin from leaking into the Bowman's space. This is supported by the obser-Eur.

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Section: Tubular Functionsupporting

confidence: 72%

Symposium Communications

1992

Clinical Chemistry and Laboratory Medicine

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“…For instance, the increased cellular sorbitol content observed in the inner medulla and papilla of animals with diabetes mellitus may be compensated by a decreased GPC content [45,51]. Interestingly, sorbitol, inositol and GPC contents are increased in the outer medulla of diabetic rats [117,139]. Whether the elevated contents of these three osmolytes are accompanied by decreased betaine contents in this kidney zone was not determined in those studies cited.…”

Section: Determinants Of Osmolyte Accumulationmentioning

confidence: 98%

“…Both in the inner medulla in vivo and in cultured renal medullary cells in AR mRNA in the kidney of diabetic rats compared with non-diabetic controls [43,44] suggests that enhanced AR gene expression contributes to the elevated AR activity. The increased medullary sorbitol contents in animals with diabetes mellitus [26,27,45,49,51,117] may be thus explained both by higher AR activity and elevated intracellular glucose concentrations. Aside from glucose, additional substances affect AR activity.…”

Section: Sorbitolmentioning

confidence: 99%

Cellular response to osmotic stress in the renal medulla

Beck¹,

Burger‐Kentischer²,

Müller³

1998

Pfl�gers Archiv European Journal of Physiology

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Cells of the renal medulla, which are exposed under normal physiological conditions to widely fluctuating extracellular solute concentrations, respond to hypertonic stress by accumulating the organic osmolytes glycerophosphorylcholine (GPC), betaine, myo-inositol, sorbitol and free amino acids. Increased intracellular contents of these osmolytes are achieved by a combination of increased uptake (myo-inositol and betaine) and synthesis (sorbitol, possibly GPC), decreased degradation (GPC) and reduced osmolyte release. In the medulla of the concentrating kidney, accumulation of organic osmolytes, which do not perturb cell function even at high concentrations, allows the maintenance of "normal" intracellular concentrations of inorganic electrolytes. Adaptation to decreasing extracellular solute concentrations, e.g. diuresis, is achieved primarily by activation of pathways allowing the efflux of organic osmolytes, and secondarily by inactivation of production (sorbitol) and uptake (betaine, myo-inositol) and stimulation of degradation (GPC). Apart from modulation of the osmolyte content, osmolality-dependent reorganization of the cytoskeleton and expression of specific stress proteins (heat shock proteins) may be further, as yet poorly characterized, components of the regulatory systems involved in the adaptation of medullary cells to osmotic stress.

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“…Chronic hyperglycaemia leads to sorbitol accumulation in a variety of tissues like peripheral neurons [10], lens and renal tubuli [35]. The initial hypothesis that sorbitol accumulation causes tissue damage is unlikely to operate in kidney [17].…”

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confidence: 99%

Alterations of glomerular matrix proteins in the pathogenesis of diabetic nephropathy

Olgemöller

Schleicher

1993

Clin Investig

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Diabetic late complications are characterized by morphological and biochemical alterations of the extracellular matrix. In particular, longstanding diabetes causes quantitative and qualitative changes in basement membrane structure of retinal and renal capilleries. Immunohistochemical investigations of diabetic kidneys with diffuse glomerulosclerosis show increased collagen type IV deposition in the mesangial matrix and decreased heparan sulfate proteoglycan content in the mesangial matrix and glomerular basement membrane as well. In nodular glomerulosclerosis normal basement membrane components are decreased or absent while the occurrence of collagen type III in this stage has been interpreted as an irreversible alteration of the glomerular structure. These changes seem to be the underlying cause for the alterations in renal functions like persistent albuminuria and proteinuria. Increased intra-and extracellular levels of glucose and its derivatives are thought to be responsible for diabetic tissue dysfunction although there are reports on possible genetic defects causing increased susceptibility to develop diabetic nephropathy. Recent results, however, focuse on the role of glucose-induced cytokine secretion as mediator for altered metabolism of glomerular matrix proteins. In vitro studies with cultured kidney cells have shown that the glucoseinduced dysregulation of the basement membrane synthesis may be mediated by a glucose dependent activation of protein kinase C. Alternatively or synergistically, the formation of AGE products formed after prolonged exposure of matrix proteins to elevated glucose may also lead to cytokine secretion subsequently inducing synthesis of cxtracellular matrix proteins. Studies in experimental animals confirm the diabetes induced dysregulation of the synthesis of extracellular matrix components on the molecular level.Abbreviations: HSPG=heparan sulfate proteoglycan; GBM= glomerular basement membrane; ECM=extracellular matrix; AGE = advanced glucosylation end products; TNF = tumor necrosis factor; bFGF=basic fibroblast growth factor

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Renal Sorbitol, myo-Inositol and Glycerophosphorylcholine in Streptozotocin-Diabetic Rats

Cited by 5 publications

References 24 publications

Symposium Communications

Symposium Communications

Cellular response to osmotic stress in the renal medulla

Alterations of glomerular matrix proteins in the pathogenesis of diabetic nephropathy

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