PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 3115161

Diabetic peripheral neuropathies.

Y Harati
View original source ↗Export metadata ↓

Abstract

Diabetic peripheral neuropathies are a group of heterogeneous syndromes with considerable morbidity. At least 50% of diabetic patients develop one or several of these neuropathies within 25 years after the diagnosis. In recent years several pathogenetic mechanisms have been proposed, with the newest findings suggesting a link between several of these hypotheses. The hypoxic hypothesis has revived the role of vascular factors in the pathogenesis of diabetic peripheral neuropathies. Although the exact role of hyperglycemia in the development of peripheral neuropathy is not known, the balance of evidence indicates that attainment and maintenance of normal blood glucose remains the cornerstone of treatment of diabetes and diabetic neuropathies. There is no convincing evidence that any of the treatments devised to correct the metabolic derangements in nerve are of sufficient value or safety to be recommended for routine use.

Explore related subjects

Aldehyde ReductaseAutonomic Nervous System DiseasesBlood GlucoseCardiovascular DiseasesDiabetes MellitusDiabetic NeuropathiesHumansMotor NeuronsNeurons, AfferentJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Y Harati. 1987. Diabetic peripheral neuropathies.. https://doi.org/10.7326/0003-4819-107-4-546

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Exploring structural feature of aldose-reductase inhibition by 5-[[2-(omega-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives employing Fujita-Ban and Hansch approach.

Designing of a highly selective, potent and safe inhibitor of aldose reductase (ALR) capable of potentially blocking the excess glucose flux through the polyol pathway that prevails under diabetic condition has been a long standing challenge. In our study, we did quantitative structure-activity relationship (QSAR) analysis, based on Fujita-Ban and classical Hansch approach, on 5-[[2-(omega-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives. Study gave structural insight into the binding mode of the molecules to the aldose reductase enzyme. The Fujita-Ban approach revealed that benzylidene thiazolidine nucleus is more potent as compare to naphthyl-methylene thiazolidine analogs. The bulkierness of naphthyl-methylene might be inquisitive with receptor. Hansch approach suggested that electron-withdrawing groups are conducive to aldose reductase inhibitory activity.

Aldehyde Reductase↗
PubMed2006

Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages.

Aldose reductase (AR; AKR1B1) a member of aldo-keto reductase super family, that we had shown earlier mediates cytotoxic signals induced by high glucose, cytokines and growth factors, also mediates the inflammatory signals induced by Gram-negative bacterial endotoxin, lipopolysaccharide (LPS). Inhibition of AR by three distinct AR inhibitors sorbinil, tolrestat or zopolrestat suppressed the LPS-induced production of inflammatory cytokines such as TNF-alpha, IL-6, IL-1beta, IFN-gamma, and chemokine MCP-1 in murine peritoneal macrophages. Inhibition of AR also prevented the production of nitric oxide, and prostaglandin E2 and expression of iNOS and Cox-2 proteins. The LPS-induced DNA binding activity of NF-kappaB and AP1 were significantly inhibited by AR inhibitors, and this effect was mediated through the inhibition of phosphorylation of IkappaB-alpha, IKK alpha/beta and PKC. These results suggest the therapeutic use of AR inhibitors as anti-inflammatory drugs.

Aldehyde Reductase↗
PubMed2006

Proteomic identification of proteins associated with the osmoregulatory transcription factor TonEBP/OREBP: functional effects of Hsp90 and PARP-1.

Hypertonicity (e.g., high NaCl) activates the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP), increasing transcription of protective genes. In the present studies, by stably expressing amino acids 1-547 of TonEBP/OREBP in HEK 293 cells and immunoprecipitating it plus associated proteins from the nuclei of cells exposed to high NaCl, we identify 14 proteins that are physically associated with TonEBP/OREBP. The associated proteins fall into several classes: 1) DNA-dependent protein kinase, both its catalytic subunit and regulatory subunit, Ku86; 2) RNA helicases, namely RNA helicase A, nucleolar RNA helicase II/Gu, and DEAD-box RNA helicase p72; 3) small or heterogeneous nuclear ribonucleoproteins (snRNPs or hnRNPs), namely U5 snRNP-specific 116 kDa protein, U5 snRNP-specific 200 kDa protein, hnRNP U, hnRNP M, hnRNP K, and hnRNP F; 4) heat shock proteins, namely Hsp90beta and Hsc70; and 5) poly(ADP-ribose) polymerase-1 (PARP-1). We confirm identification of most of the proteins by Western analysis and also demonstrate by electrophoretic mobility-shift assay that they are present in the large complex that binds specifically along with TonEBP/OREBP to its cognate DNA element. In addition, we find that PARP-1 and Hsp90 modulate TonEBP/OREBP activity. PARP-1 expression reduces TonEBP/OREBP transcriptional activity and the activity of its transactivating domain. Hsp90 enhances those activities and sustains the increased abundance of TonEBP/OREBP protein in cells exposed to high NaCl.

Aldehyde Reductase↗