The Metabolic Role of GRK2 in Insulin Resistance and Associated Conditions

Sorriento, Daniela; Rusciano, Maria Rosaria; Visco, Valeria; Fiordelisi, Antonella; Cerasuolo, F; Poggio, Paolo; Ciccarelli, Michele; Iaccarino, Guido

doi:10.3390/cells10010167

Cited by 17 publications

(16 citation statements)

References 116 publications

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“…Heart failure (HF) shows phases of exacerbation interrupted by periods of clinical stability. Despite many pharmacological advances, morbidity and mortality in HF remain an important burden to patients, caregivers, and national healthcare systems ( 1 – 3 ). Advanced HF, defined as severe symptoms despite optimal medical therapy (OMT) and device, affects up to 25% of patients with HF ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

Visco

Esposito

Manzo

et al. 2022

Front. Cardiovasc. Med.

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During the last years, the management of heart failure (HF) made substantial progress, focusing on device-based therapies to meet the demands of this complex syndrome. In this case report, we present a multistep approach to deal with HF. Specifically, we report the first patient subjected to the implantation of both Optimizer Smart® (Impulse Dynamics Inc., Marlton, NJ, USA) and CardioMEMS devices. A 72-year-old male patient with HF and reduced ejection fraction (HFrEF) was admitted to our cardiology department in January 2021, following a progressive shortening of the time between hospitalizations for levosimendan infusions. Specifically, the patient was monitored daily by CardioMEMS, and a strategy of levosimendan infusions guided by the device had been adopted. He was also a carrier of MitraClips and cardiac resynchronization therapy defibrillator (CRT-D) and had optimized HF medical therapy. In January 2021, the patient implanted Optimizer Smart® device for cardiac contractility modulation (CCM) therapy because of poor response to therapy and elevated pulmonary artery pressure (PAP). CCM significantly reduced PAP values following discharge (systolic PAP 33.67 ± 2.92 vs. 40.6 ± 3.37 mmHg, diastolic PAP 14.5 ± 2.01 vs. 22.5 ± 2.53 mmHg, mean PAP 22.87 ± 2.20 vs. 30.9 ± 2.99 mmHg, HR 60.93 ± 1.53 vs. 80.83 ± 3.66 bpm; p < 0.0001), with persisting effect at 9 months. The usefulness of CCM is objectively demonstrated for the first time by continuous invasive monitoring of PAP by CardioMEMS, which can suggest the correct timing for CCM implantation.

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Section: Introductionmentioning

confidence: 99%

A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

Visco

Esposito

Manzo

et al. 2022

Front. Cardiovasc. Med.

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“…The TyG index is a reliable and simple diagnostic indicator of insulin resistance [ 29 , 30 ]. When the body is in the IR state, the PI3K pathway is affected, with the MAPK pathway unaffected; and the balance between the two pathways is therefore disrupted [ 31 , 32 ]. Inhibition of the PI3K pathway leads to a reduction in the production of NO in endothelial cells, which in turn reduces ED and glucose transporters and results in a reduction in glucose uptake [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Triglyceride-Glucose Index for the Diagnosis of Metabolic Syndrome: A Cross-Sectional Study of 298,652 Individuals Receiving a Health Check-Up in China

Jiang

et al. 2022

International Journal of Endocrinology

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Objective. We herein aim to explore the relationship between the triglyceride-glucose (TyG) index and metabolic syndrome (MS). Methods. We enrolled 298,652 individuals with an average age of 47.08 ± 12.94 years and who underwent health check-ups at the First Affiliated Hospital of Wuhu Wannan Medical College in this cross-sectional study from 2014 to 2016. We enlisted 125,025 women (41.86%) and 173,627 men (58.14%). The survey information included a questionnaire survey, a physical examination, and a laboratory examination. Results. The prevalence of MS increased gradually in the TyG-index subgroups (Q1, TyG <8.30; Q2, 8.30≤ TyG <8.83; and Q3, TyG ≥8.83). We noted significant differences in hypertension, hyperlipidemia, hyperglycemia, sex, age, body mass index (BMI), smoking and drinking habits, and estimated glomerular filtration rate between the TyG-index subgroups. Multiclass logistic regression analysis showed that the group with TyG <8.30 was the reference group, and the 8.30≤ TyG <8.83 and the TyG ≥8.83 groups exhibited a higher TyG index with MS, and a lower TyG index without MS disease. In the linear curve analysis of the TyG index and MS components, BMI, systolic blood pressure, and diastolic blood pressure showed upward trends, while high-density lipoprotein cholesterol showed no obvious trend in the TyG index at a range of 7.8–11.0. Receiver operating characteristic analysis was used to evaluate the predictive value of the TyG index, triglycerides, and fasting blood glucose for MS, and we found that the area under the TyG index curve was the largest (AUC = 0.89). Conclusion. There were associations between the TyG index and MS and its components, and the TyG index is therefore of great value in the early diagnosis of MS.

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“…The result seemed to conflict with 18 F-FDG uptake and Western blot results since the Akt/mTOR pathway was upregulated in Huh7/SR cells. Akt is known to suppress glycogen synthase kinase-3 (GSK-3) and enhance glycogen synthesis [ 69 ]. HK2, GAPDH, and PKM2 are the glycolytic enzymes, and elevated glycolysis is related to tumor progression and treatment resistance [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Orlistat Resensitizes Sorafenib-Resistance in Hepatocellular Carcinoma Cells through Modulating Metabolism

Shueng

Chan

Lin

et al. 2022

IJMS

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Sorafenib is one of the options for advanced hepatocellular carcinoma treatment and has been shown to extend median overall survival. However, sorafenib resistance often develops a few months after treatment. Hence, developing various strategies to overcome sorafenib resistance and understand the possible mechanisms is urgently needed. We first established sorafenib-resistant hepatocellular carcinoma (HCC) cells. Then, we found that sorafenib-resistant Huh7 cells (Huh7/SR) exhibit higher glucose uptakes and express elevated fatty acid synthesis and glucose metabolism-related proteins than their parental counterparts (Huh7). The current study investigated whether sorafenib resistance could be reversed by suppressing fatty acid synthesis, using a fatty acid synthase (FASN) inhibitor, orlistat, in HCC cells. FASN inhibition-caused changes in protein expressions and cell cycle distribution were analyzed by Western blot and flow cytometry, and changes in glucose uptakes were also evaluated by 18F-FDG uptake. Orlistat remarkably enhanced the cytotoxicity of sorafenib in both Huh7 and Huh7/SR cells, and flow cytometry showed that combination treatment significantly increased the sub-G1 population in both cell lines. Western blot revealed that the combination treatment effectively increased the ratio of Bax/Bcl-2 and decreased expressions of pERK; additionally, the combination treatment also strongly suppressed fatty acid synthesis-related proteins (e.g., FASN and SCD) in both cell lines. Lastly, the 18F-FDG uptake was repressed by the combination treatment in both cell lines. Our results indicated that orlistat-mediated FASN inhibition could overcome sorafenib resistance and enhance cell killing in HCC by changing cell metabolism.

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The Metabolic Role of GRK2 in Insulin Resistance and Associated Conditions

Cited by 17 publications

References 116 publications

A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

Triglyceride-Glucose Index for the Diagnosis of Metabolic Syndrome: A Cross-Sectional Study of 298,652 Individuals Receiving a Health Check-Up in China

Orlistat Resensitizes Sorafenib-Resistance in Hepatocellular Carcinoma Cells through Modulating Metabolism

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