Insulin resistance, obesity and the metabolic syndrome. Is there a therapeutic role for endothelin-1 antagonists?

Shaw, SG; Boden, PJ (2005). Insulin resistance, obesity and the metabolic syndrome. Is there a therapeutic role for endothelin-1 antagonists? Current vascular pharmacology, 3(4), 359-63.. San Francisco, Calif.: Bentham Science Publishers

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There is increasing evidence to suggest that chronic activation of the endothelin-1 system can lead to heterologous desensitization of the glucose-regulatory and mitogenic actions of insulin with subsequent development of glucose intolerance, hyperinsulinemia, impaired endothelial function and exacerbation of cardiovascular disease. Effects are mediated through a variety of mechanisms that include attenuation of key insulin signalling pathways and decreased tyrosine phosphorylation of insulin receptor substrates IRS-1, SHC and G alpha q/11. Other actions involve hemodynamic changes leading to reduced delivery of insulin and glucose to peripheral tissues as well as enhanced hepatic glycogenolysis, decreased glucose-transporter translocation and modulation of various adipokines that regulate insulin action. Overall the data suggest that ET-1 antagonists may provide an effective means of improving cardiac dysfunction and favourably influencing glucose tolerance in obese humans and patients with early insulin sensitivity where there is clear evidence for activation of the ET-1 system. Although most effects of ET-1 that modulate mechanisms leading to glucose intolerance appear to involve the ETA receptor subtype recent data indicates that combined ETA/ETB receptor antagonists may function as effectively as selective ETA blockers. Prospective trials are needed to assess whether ET-1 antagonists, either alone or in combination, are superior to other more conventional therapies such as insulin sensitizers and to evaluate effects of combined treatments on the development of insulin resistance and the progression of diabetes. Early screening of patients at risk for evidence of ET-1 activation would help to identify subjects who may benefit most from such treatment.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital [discontinued] > Forschungsgruppe Vasoaktive Peptide [discontinued]

UniBE Contributor:

Shaw, Sidney

ISSN:

1570-1611

ISBN:

16248779

Publisher:

Bentham Science Publishers

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:58

Last Modified:

05 Dec 2022 14:18

PubMed ID:

16248779

URI:

https://boris.unibe.ch/id/eprint/24999 (FactScience: 54599)

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