Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients

Sidharta, Patricia N.; Wagner, Frank; Bohnemeier, Holger; Jungnik, Arvid; Halabi, Atef; Krähenbühl, Stephan; Chadha‐Boreham, Harbajan; Dingemanse, Jasper

doi:10.1016/j.clpt.2006.05.013

Cited by 65 publications

(52 citation statements)

References 43 publications

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“…Subnetwork A ( Figure 5A) and B ( Figure 5B) included quite a number of previously reported T2D-related genes: Tcf4 and Dcc [32]; Cd3d [33], Uts2r [34] and Map2k1 [35]. Subnetwork C ( Figure 5C) was the largest reversed DCL-organized module and it contained an interesting four-gene-circuit (including Arpc5l, Tra1, Mcm3ap, and Hspe1) of consistent negative-topositive correlation reversal.…”

Section: Re-analyzing a T2d Dataset From The Perspective Of Differentmentioning

confidence: 74%

RSEM: Accurate Transcript Quantification from RNA-Seq Data With or Without a Reference Genome

2014

Bioinformatics

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Background: Differential coexpression analysis (DCEA) is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance. Results: We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links). Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D) expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis. Conclusions: This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum.

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Section: Re-analyzing a T2d Dataset From The Perspective Of Differentmentioning

confidence: 74%

RSEM: Accurate Transcript Quantification from RNA-Seq Data With or Without a Reference Genome

2014

Bioinformatics

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“…Unfortunately, to date, human studies using palosuran have been largely inconclusive. Oral palosuran treatment of hypertensive type 2 diabetic nepropathy patients with 125 mg, twice daily for 13.5 days when combined with ACE inhibitors or ARBs, decreased 24-h urinary albumin excretion rate (110). However, palosuran did not affect important renal hemodynamic parameters, such as glomerular filtration rate and renal blood flow (110).…”

Section: Potential Therapeutic Applicationsmentioning

confidence: 94%

“…Oral palosuran treatment of hypertensive type 2 diabetic nepropathy patients with 125 mg, twice daily for 13.5 days when combined with ACE inhibitors or ARBs, decreased 24-h urinary albumin excretion rate (110). However, palosuran did not affect important renal hemodynamic parameters, such as glomerular filtration rate and renal blood flow (110). In a subsequent study in type 2 diabetics, palosuran demonstrated no clinically significant effects on ␤-cell secretory capacity and no effects on first-and secondphase insulin response (109).…”

Section: Potential Therapeutic Applicationsmentioning

confidence: 95%

Role of urotensin II in health and disease

Ross

McKendy

Giaid

2010

American Journal of Physiology-Regulatory, Integrative and Comp

126

107

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Urotensin II (UII) is an 11 amino acid cyclic peptide originally isolated from the goby fish. The amino acid sequence of UII is exceptionally conserved across most vertebrate taxa, sharing structural similarity to somatostatin. UII binds to a class of G protein-coupled receptor known as GPR14 or the urotensin receptor (UT). UII and its receptor, UT, are widely expressed throughout the cardiovascular, pulmonary, central nervous, renal, and metabolic systems. UII is generally agreed to be the most potent endogenous vasoconstrictor discovered to date. Its physiological mechanisms are similar in some ways to other potent mediators, such as endothelin-1. For example, both compounds elicit a strong vascular smooth muscle-dependent vasoconstriction via Ca 2ϩ release. UII also exerts a wide range of actions in other systems, such as proliferation of vascular smooth muscle cells, fibroblasts, and cancer cells. It also 1) enhances foam cell formation, chemotaxis of inflammatory cells, and inotropic and hypertrophic effects on heart muscle; 2) inhibits insulin release, modulates glomerular filtration, and release of catecholamines; and 3) may help regulate food intake and the sleep cycle. Elevated plasma levels of UII and increased levels of UII and UT expression have been demonstrated in numerous diseased conditions, including hypertension, atherosclerosis, heart failure, pulmonary hypertension, diabetes, renal failure, and the metabolic syndrome. Indeed, some of these reports suggest that UII is a marker of disease activity. As such, the UT receptor is emerging as a promising target for therapeutic intervention. Here, a concise review is given on the vast physiologic and pathologic roles of UII.UT receptor; somatostatin; human; experimental animals; autocrine/paracrine UROTENSIN II (UII) was initially isolated from the urophysis of the goby fish (Gillichthys mirabilis) (97). The peptide was subsequently isolated from the white sucker (Catostomus commersoni) and the carp (Cyprinus carpio). Although there were variations in the amino acid sequence near the amino terminus, in both species the UII molecule retained the COOH-terminal cyclic sequence: -Cys

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“…However, clinical trials led to divergent results (Desai et al, 2008;Tsoukas et al, 2011). One study indicates that, in hypertensive T2DM patients affected by nephropathy, palosuran (125 mg twice daily) reduces albuminuria, suggesting that blockage of UT could be a therapeutic approach for the treatment of diabetic nephropathy (Sidharta et al, 2006). However, the authors subsequently found that palosuran does not improve insulin secretion, insulin sensitivity, and glycemia in T2DM (Sidharta et al, 2009).…”

Section: E Effect Of Urotensin Ii/urotensin Ii-related Peptide On Thmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

et al. 2014

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Pharmacodynamics and pharmacokinetics of the urotensin II receptor antagonist palosuran in macroalbuminuric, diabetic patients

Cited by 65 publications

References 43 publications

RSEM: Accurate Transcript Quantification from RNA-Seq Data With or Without a Reference Genome

RSEM: Accurate Transcript Quantification from RNA-Seq Data With or Without a Reference Genome

Role of urotensin II in health and disease

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

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