Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia–Reperfusion Injury in Diet-Induced Obesity

Oi, Yuhei; Nagoshi, Tomohisa; Kimura, Haruka; Tanaka, Yoshiro; Yoshii, Akira; Yasutake, Rei; H, Takahashi; Kashiwagi, Yusuke; Tanaka, Toshikazu; Tachibana, Toshiaki; Yoshimura, Michihiro

doi:10.3390/ijms23158373

Cited by 7 publications

(6 citation statements)

References 61 publications

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“… 17 In addition, we reported that in mice fed a high‐fat diet, the administration of exogenous A‐type natriuretic peptide ameliorated systemic insulin resistance by attenuating hepatic steatosis and inducing adipose tissue browning and furthermore ameliorated myocardial insulin resistance and protected against ischaemia–reperfusion injury. 18 , 19 In the present study, the levels of liver enzymes, such as ALT, ALP, and γ‐GTP, tended to decrease after ARNI treatment. However, the SEM analyses failed to show a significant relationship between the initiation of ARNI treatment and improvement in the liver function due to missing data.…”

Section: Discussionsupporting

confidence: 55%

“…Moreover, we previously reported that natriuretic peptides, which are increased by neprilysin inhibition, could halt the progression to diabetes by improving insulin resistance under the metabolically harmful condition of heart failure 17 . In addition, we reported that in mice fed a high‐fat diet, the administration of exogenous A‐type natriuretic peptide ameliorated systemic insulin resistance by attenuating hepatic steatosis and inducing adipose tissue browning and furthermore ameliorated myocardial insulin resistance and protected against ischaemia–reperfusion injury 18,19 . In the present study, the levels of liver enzymes, such as ALT, ALP, and γ‐GTP, tended to decrease after ARNI treatment.…”

Section: Discussionsupporting

confidence: 51%

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Effects of angiotensin receptor‐neprilysin inhibitor on insulin resistance in patients with heart failure

et al. 2023

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Aims Although the haemodynamic effects of angiotensin receptor‐neprilysin inhibitor (ARNI) on patients with heart failure have been demonstrated, the effect on glucose metabolism has not been fully elucidated. We retrospectively investigated the effect of ARNI on abnormal glucose metabolism in patients with stable chronic heart failure using an additional structural equation model (SEM) analysis. Methods We analysed 34 patients who regularly visited to the outpatient department of our institute with heart failure from October 2021 and July 2022 and who were taking angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Seventeen patients switched from ACE inhibitors or ARBs to an ARNI (ARNI group), and the other 17 patients continued treatment with ACE inhibitors or ARBs (control group). Results At baseline, although the ARNI group included fewer patients with heart failure with preserved ejection fraction in comparison with the control group (P = 0.004), patients with heart failure with mildly reduced ejection fraction, and heart failure with reduced ejection fraction were mostly biased towards the ARNI group (although not statistically significant). The baseline insulin resistance in the ARNI group was already significantly higher in comparison with the control group [fasting blood insulin, 9.7 (7.4, 11.6) vs. 7.8 (5.2, 9.2) μU/mL, P = 0.033; homoeostasis model assessment of insulin resistance (HOMA‐IR), 3.10 (1.95, 4.19) vs. 2.02 (1.56, 2.42), P = 0.014]. Three months later, the fasting blood insulin and the HOMA‐IR levels were both found to have decreased in comparison with the baseline values [baseline to 3 months: insulin, 9.7 (7.4, 11.6) to 7.3 (4.6, 9.4) μU/mL, P < 0.001; HOMA‐IR, 3.10 (1.95, 4.19) to 1.96 (1.23, 3.09), P < 0.001]. An additional SEM analysis demonstrated that the initiation of ARNI had caused a reduction in the fasting blood insulin and the HOMA‐IR levels at 3 months independently of the baseline fasting blood insulin and HOMA‐IR levels, respectively. Similarly, the initiation of ARNI resulted in a significant reduction in serum uric acid levels (6.28 ± 0.35 to 5.80 ± 0.30 mg/dL, P = 0.008). Conclusions In conclusion, even in a short period of only 3 months, the administration of ARNI improved insulin resistance and consequently reduced the serum uric acid levels in patients with stable chronic heart failure. Although the ARNI group already had high insulin resistance at baseline, an additional SEM analysis revealed that the decreased insulin resistance was truly due to the effect of ARNI.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 51%

Effects of angiotensin receptor‐neprilysin inhibitor on insulin resistance in patients with heart failure

et al. 2023

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“…A continuous subcutaneous infusion of saline was conducted in the DM + saline and DM + NPRC −/− groups, respectively, and infusion of ANP (ANP1-28, MCE, USA; 0.5 μg/kg per minute), BNP (BNP1-32, MCE, USA; 0.03 μg/kg per minute), and CNP (CNP1-22, TargetMol, USA; 0.1 μg/kg per minute) was performed in the DM + ANP, DM + BNP, and DM + CNP groups, respectively. The dose of ANP, BNP, and CNP was chosen by referring to previous studies (27,(54)(55)(56)(57)(58). After 28 days of infusion, these mice were euthanized for morphological and pathological detection.…”

Section: Animal Protocolsmentioning

confidence: 99%

NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways

Meng

Wang

et al. 2023

Sci. Adv.

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Cardiac fibrosis plays a key role in the progression of diabetic cardiomyopathy (DCM). Previous studies demonstrated the cardioprotective effects of natriuretic peptides. However, the effects of natriuretic peptide receptor C (NPRC) on cardiac fibrosis in DCM remains unknown. Here, we observed that myocardial NPRC expression was increased in mice and patients with DCM. NPRC −/− diabetic mice showed alleviated cardiac fibrosis, as well as improved cardiac function and remodeling. NPRC knockdown in both cardiac fibroblasts and cardiomyocytes decreased collagen synthesis and proliferation of cardiac fibroblasts. RNA sequencing identified that NPRC deletion up-regulated the expression of TGF-β–induced factor homeobox 1 (TGIF1), which inhibited the phosphorylation of Smad2/3. Furthermore, TGIF1 up-regulation was mediated by the activation of cAMP/PKA and cGMP/PKG signaling induced by NPRC deletion. These findings suggest that NPRC deletion attenuated cardiac fibrosis and improved cardiac remodeling and function in diabetic mice, providing a promising approach to the treatment of diabetic cardiac fibrosis.

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“…It has been previously demonstrated that exercise-induced cardiac stress resistance is at least in part mediated through mitochondrial adaptation [ 39 , 40 , 41 ]. Musclin has been shown to govern exercise-induced mitochondrial biogenesis in skeletal muscles [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Myokine Musclin Is Critical for Exercise-Induced Cardiac Conditioning

Harris

Zeng

Zhu

et al. 2023

IJMS

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This study investigates the role and mechanisms by which the myokine musclin promotes exercise-induced cardiac conditioning. Exercise is one of the most powerful triggers of cardiac conditioning with proven benefits for healthy and diseased hearts. There is an emerging understanding that muscles produce and secrete myokines, which mediate local and systemic “crosstalk” to promote exercise tolerance and overall health, including cardiac conditioning. The myokine musclin, highly conserved across animal species, has been shown to be upregulated in response to physical activity. However, musclin effects on exercise-induced cardiac conditioning are not established. Following completion of a treadmill exercise protocol, wild type (WT) mice and mice with disruption of the musclin-encoding gene, Ostn, had their hearts extracted and exposed to an ex vivo ischemia-reperfusion protocol or biochemical studies. Disruption of musclin signaling abolished the ability of exercise to mitigate cardiac ischemic injury. This impaired cardioprotection was associated with reduced mitochondrial content and function linked to blunted cyclic guanosine monophosphate (cGMP) signaling. Genetic deletion of musclin reduced the nuclear abundance of protein kinase G (PKGI) and cyclic adenosine monophosphate (cAMP) response element binding (CREB), resulting in suppression of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and its downstream targets in response to physical activity. Synthetic musclin peptide pharmacokinetic parameters were defined and used to calculate the infusion rate necessary to maintain its plasma level comparable to that observed after exercise. This infusion was found to reproduce the cardioprotective benefits of exercise in sedentary WT and Ostn-KO mice. Musclin is essential for exercise-induced cardiac protection. Boosting musclin signaling might serve as a novel therapeutic strategy for cardioprotection.

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Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia–Reperfusion Injury in Diet-Induced Obesity

Cited by 7 publications

References 61 publications

Effects of angiotensin receptor‐neprilysin inhibitor on insulin resistance in patients with heart failure

Effects of angiotensin receptor‐neprilysin inhibitor on insulin resistance in patients with heart failure

NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways

Myokine Musclin Is Critical for Exercise-Induced Cardiac Conditioning

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