15th Golgi lecture: from hyperglycaemia to the dysregulation of vascular remodelling in diabetes.

Abstract:

:Hyperglycaemia has been shown to play a central part in diabetic vascular disease, which is also influenced by individual background. Hyperglycaemia initiates the pathogenetic sequence through a series of interrelated biochemical abnormalities, including increased flux through the polyol and hexosamine pathways, oxidative stress, AGE formation and protein kinase C activation. These abnormalities are capable of modifying the function of resident and non-resident vascular cells by changing their production pattern of several autocrine and paracrine factors, including growth, vasoactive and coagulation factors and adhesion molecules. These mediators profoundly impair the physiologic turnover of the vessel wall, thus leading to an abnormal process of vascular remodelling, with alterations in cell and matrix turnover and contacts, vascular tone and permeability and coagulation pattern. This process has distinct features depending on the target tissue. The hallmark of nephropathy is an abnormal accumulation of extracellular matrix within the mesangium, sustained by an upregulation of TGF-beta, possibly triggered by a local activation of the renin-angiotensin system. The central pathological lesion in retinopathy is retinal ischaemia due to the formation of acellular capillaries. The resulting vascular endothelial growth factor-dependent neovascularization is a detrimental phenomenon leading to the formation of noncompetent vessels. Conversely, in macrovascular disease, arterial occlusion resulting from plaque formation with superimposed thrombosis elicits an angiogenic response which is impaired, but generates competent vessels, potentially compensating for reduced flow. Thus, upstream interventions interrupting the pathogenetic sequence at the level of hyperglycaemia (and related biochemical events) are the most effective, whereas downstream interventions should be targeted to the tissue affected.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Di Mario U,Pugliese G

doi

10.1007/s001250051676

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

674-92

issue

6

eissn

0012-186X

issn

1432-0428

journal_volume

44

pub_type

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    pub_type: 杂志文章

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    更新日期:1987-09-01 00:00:00

  • Tolbutamide-induced changes of the DNA, protein and insulin content and the secretory activity of isolated rat pancreatic islets.

    abstract::Following prolonged administration of tolbutamide the DNA- and protein content per islet was enhanced but the IRI content per islet was diminished. Glucose-induced (2.0, 8.0 or 16.6 mM) and leucine-induced (12.5 or 25.0 mM) IRI release from isolated islets, as well as 14C02-production from U-14C glucose, were decrease...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00422395

    authors: Schauder P,Frerichs H

    更新日期:1975-08-01 00:00:00

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    abstract:AIMS/HYPOTHESIS:African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery ...

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    pub_type: 杂志文章

    doi:10.1007/s00125-005-0017-2

    authors: Freedman BI,Hsu FC,Langefeld CD,Rich SS,Herrington DM,Carr JJ,Xu J,Bowden DW,Wagenknecht LE

    更新日期:2005-12-01 00:00:00

  • Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

    abstract::N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velo...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00418340

    authors: Sagara M,Satoh J,Wada R,Yagihashi S,Takahashi K,Fukuzawa M,Muto G,Muto Y,Toyota T

    更新日期:1996-03-01 00:00:00