Search for a biochemical basis of diabetic microangiopathy

Rg, Spiro

doi:10.1007/bf01221959

Cited by 191 publications

(73 citation statements)

References 85 publications

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“…We could show increased solubility of GBM but no apparent change in amino acid composition. Whether reducible crosslinks, similar to those found in collagen, are present in GBM is a matter of dispute since, although their presence has been reported [ 151, similar procedures have failed to detect them [3]. One explanation for this discrepancy may be that reducible crosslinks present in young animals are converted to non-reducible crosslinks in older animals [ 161.…”

Section: Discussionmentioning

confidence: 99%

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Modification of glomerular basement membrane following the administration of the lathyrogen aminoacetonitrile to rats

Taylor¹,

Price²

1980

FEBS Letters

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Section: Discussionmentioning

confidence: 99%

“…Glomerular basement membrane (GBM) is a member of the collagen family and contains collagen-like and polar regions [3]. When GBM is solubilised in sodium dodecyl sulphate (SDS) and 2-mercaptoethanol a residue, accounting for 20% of the total protein of the membrane, remains.…”

Section: Introductionmentioning

confidence: 99%

Modification of glomerular basement membrane following the administration of the lathyrogen aminoacetonitrile to rats

Taylor¹,

Price²

1980

FEBS Letters

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“…2A, the phytoestrogen genistein, a general inhibitor of tyrosine kinases (35), completely prevented the increase in HK activity following HB-EGF treatment. This effect was maximal at genistein concentrations Ն25 M (apparent IC 50 2 M) and was not accompanied by a corresponding change in basal HK activity ( Fig. 2A).…”

Section: Fig 1 Hb-egf Increases Mesangial Cell Hk Activity In a Conmentioning

confidence: 93%

Regulation of Mesangial Cell Hexokinase Activity and Expression by Heparin-binding Epidermal Growth Factor-like Growth Factor

Robey¹,

Ma²,

Santos³

et al. 2002

Journal of Biological Chemistry

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Heparin-binding epidermal growth factor -like growth factor (HB-EGF) expression and hexokinase (HK) activity are increased in various pathologic renal conditions. Although the mitogenic properties of HB-EGF have been well characterized, its effects on glucose (Glc) metabolism have not. We therefore examined the possibility that HB-EGF might regulate HK activity and expression in glomerular mesangial cells, which constitute the principal renal cell type affected by a variety of pathologic conditions. Protein kinase C (PKC)-dependent classic mitogenactivated protein kinase (MAPK) pathway activation has been associated with increased HK activity in this cell type, so we also examined dependence upon these signaling intermediates. HB-EGF (>10 nM) increased total HK activity over 50% within 12-24 h, an effect mimicked by other EGF receptor agonists, but not by IGF-1 or elevated Glc. EGF receptor and classic MAPK pathway antagonists prevented this increase, as did general inhibitors of gene transcription and protein synthesis. Both HB-EGF and phorbol esters activated the classic MAPK pathway, albeit via PKC-independent and PKC-dependent mechanisms, respectively. Both stimuli were associated with increased HK activity, selectively increased HKII isoform expression, and increased Glc metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose phosphate pathway. HB-EGF thus constitutes a novel regulator of mesangial cell HK activity and Glc metabolism. HKII is the principal regulated isoform in these cells, as it is in insulin-sensitive peripheral tissues, such as muscle. However, the uniform requirement for classic MAPK pathway activation distinguishes HKII regulation in mesangial cells from that observed in muscle. These findings suggest a novel mechanism whereby growth factors may couple metabolism to glomerular injury.

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“…There is depression in the synthesis of glycogen, lipid and protein in the cells of those tissues that are normally dependent on insulin. Spire in 1976 (1) pointed out that although diabetes has classically been considered a disease of glucose underutilization there are now many indications that in diabetes a shunting of glucose from insulin dependent pathways to those not requiring this hormone may take place.…”

Section: Glucose Overutilization In Diabetesmentioning

confidence: 99%

Regulation of metabolic pathways in liver and kidney during experimental diabetes: Effects of antidiabetic compounds

Baquer

Gupta

Raju

1998

Indian J Clin Biochem

102

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ABSTRACT:Diabetes has been classified as a disease of glucose overproduction by tissues, mainly liver and glucose underutilization by insulin requiring tissues like liver, adipose and muscle due to lack of insulin. There is, however, glucose over utilization in tissues not dependent on insulin for glucose transport like kidney, nerve and brain. There are serious complications due to this excess glucose in these tissues and their reversal is important for a good metabolic control and normalisation of other parameters. Insulin, trace metals and some plant extracts have been used to see the reversal effects of the complications of diabetes in liver and kidney in experimental diabetes. Almost complete reversal of the metabolic changes has been achieved in the activities of key enzymes of metabolic pathways in liver and kidney and an effective glucose control has been achieved suggesting a combination of therapies in the treatment of metabolic disturbance of the diabetic state.

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Search for a biochemical basis of diabetic microangiopathy

Cited by 191 publications

References 85 publications

Modification of glomerular basement membrane following the administration of the lathyrogen aminoacetonitrile to rats

Modification of glomerular basement membrane following the administration of the lathyrogen aminoacetonitrile to rats

Regulation of Mesangial Cell Hexokinase Activity and Expression by Heparin-binding Epidermal Growth Factor-like Growth Factor

Regulation of metabolic pathways in liver and kidney during experimental diabetes: Effects of antidiabetic compounds

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