Relaxin expression correlates significantly with serum fibrinogen variation in response to antidiabetic treatment in women with type 2 diabetes mellitus

Schöndorf, Thomas; Lübben, G.; Hoopmann, Markus; Borchert, Margret; Forst, Thomas; Hohberg, C.; Löbig, Mirjam; Armbruster, Franz-Paul; Roth, W.; Grabellus, Martin; Pfützner, A. H.

doi:10.1080/09513590701447998

Cited by 14 publications

(7 citation statements)

References 29 publications

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“…However, in one study that included nondiabetic patients with known cardiovascular disease, pioglitazone resulted in a nonsignificant trend toward increased ESR [41]. The decrease in IL-6 concentrations we observed after pioglitazone therapy is mechanistically concordant with the reduction in CRP that occurred, but factors driving ESR may not have been altered as much [42,43]. In contrast to IL-6, TNF-α concentrations were not significantly affected by pioglitazone, raising the possibility that pioglitazone may have greater effects on IL-6 than on TNF-α.…”

Section: Discussionmentioning

confidence: 62%

Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial

et al. 2013

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IntroductionRheumatoid arthritis (RA), a chronic inflammatory disease, is associated with insulin resistance. Experimental evidence indicates that the relationship between insulin resistance and inflammation is bidirectional: Inflammation promotes insulin resistance, and insulin resistance promotes inflammation. Therefore, we examined the hypothesis that pioglitazone, a thiazolidinedione peroxisome proliferator-activated receptor γ agonist, would decrease inflammation and disease activity and improve insulin resistance in patients with RA.MethodsIn a single-center, randomized, double-blind, placebo-controlled crossover study patients with RA (N = 34) receiving stable therapy were randomized to also receive either pioglitazone 45 mg daily (n = 17) or matching placebo (n = 17) for eight weeks. This was followed by a four-week washout period and alternative treatment for eight weeks. Outcomes included change in Disease Activity Score in 28 joints (DAS28) score, individual components of the DAS28 score and homeostatic model assessment for insulin resistance (HOMA). Intention-to-treat analysis and linear mixed-effects models were used.ResultsPatients had a mean (±SD) age of 51 (±14.2) years, 82.4% were female and baseline DAS28 high-sensitivity C-reactive protein (DAS28-CRP) was 4.58 (±1.1) units. Addition of pioglitazone was associated with a 9.3% reduction (95% confidence interval (CI) = 0.17% to 17.6%) in DAS28-CRP (P = 0.046), but no significant change in DAS28 erythrocyte sedimentation rate (DAS28-ESR) (P = 0.92). There was a 10.7mm (95% CI = 0.4 to 20.9 mm) improvement in patient-reported global health (P = 0.042), a 48.6% decrease (95% CI = 27.6% to 63.5%) in CRP (P < 0.001) and a 26.4% decrease (95% CI = 3.7% to 43.8%) in insulin resistance as measured by HOMA (P = 0.025), but no significant reduction in swollen or tender joint count or in ESR (all P > 0.05). Lower-extremity edema was more common during pioglitazone treatment (16%) than placebo (0%).ConclusionAddition of pioglitazone to RA therapy improves insulin resistance and modestly reduces RA disease activity measured by DAS28-CRP and two of its components, including patient-reported global health and CRP, but not DAS28-ESR or ESR.Trial registrationNCT00763139

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Section: Discussionmentioning

confidence: 62%

Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial

et al. 2013

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“…For example, plasma RLX levels have been shown to be related to insulin sensitivity and serum fibrinogen levels in female patients with type 2 diabetes mellitus [12,13], suggesting, that this „"insulin-like" hormone is indeed related to changes in metabolism.…”

Section: Discussionmentioning

confidence: 99%

The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease

et al. 2009

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The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO < 1.96 W) had higher NTproANP and NTproB-NP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.

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“…RLX was found in a variety of tissues including several non‐reproductive organs16. RLX acting as a pleiotropic hormone17 protects heart18–24, lungs25, and kidney26–28 due to its strong antifibrotic and vasodilator activity29–35. Furthermore, RLX may be useful in the treatment of pancreatitis36, preeclampsia37, inflammation38, and in wound healing (angiogenesis)39.…”

Section: Introductionmentioning

confidence: 99%

An optimized chemical synthesis of human relaxin‐2

Gatos

Vasileiou

Barlos

2010

Journal of Peptide Science

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Human gene 2 relaxin (RLX) is a member of the insulin superfamily and is a multi-functional factor playing a vital role in pregnancy, aging, fibrosis, cardioprotection, vasodilation, inflammation, and angiogenesis. RLX is currently applied in clinical trials to cure among others acute heart failure, fibrosis, and preeclampsia. The synthesis of RLX by chemical methods is difficult because of the insolubility of its B-chain and the required laborious and low yielding site-directed combination of its A (RLXA) and B (RLXB) chains. We report here that oxidation of the Met(25) residue of RLXB improves its solubility, allowing its effective solid-phase synthesis and application in random interchain combination reactions with RLXA. Linear Met(O)(25)-RLX B-chain (RLXBO) reacts with a mixture of isomers of bicyclic A-chain (bcRLXA) giving exclusively the native interchain combination. Applying this method Met(O)(25)-RLX (RLXO) was obtained in 62% yield and was easily converted to RLX in 78% yield, by reduction with ammonium iodide.

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Relaxin expression correlates significantly with serum fibrinogen variation in response to antidiabetic treatment in women with type 2 diabetes mellitus

Cited by 14 publications

References 29 publications

Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial

Peroxisome proliferator-activated receptor γ agonist effect on rheumatoid arthritis: a randomized controlled trial

The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease

An optimized chemical synthesis of human relaxin‐2

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