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4. The p66Shc Redox Protein and the Emerging Complications of Diabetes

Author

Biondi, Giuseppina, primary, Marrano, Nicola, additional, Borrelli, Anna, additional, Rella, Martina, additional, D’Oria, Rossella, additional, Genchi, Valentina Annamaria, additional, Caccioppoli, Cristina, additional, Cignarelli, Angelo, additional, Perrini, Sebastio, additional, Laviola, Luigi, additional, Giorgino, Francesco, additional, and Natalicchio, Annalisa, additional

Published
2023
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5. The p66 Shc Redox Protein and the Emerging Complications of Diabetes.

Author

Biondi, Giuseppina, Marrano, Nicola, Borrelli, Anna, Rella, Martina, D'Oria, Rossella, Genchi, Valentina Annamaria, Caccioppoli, Cristina, Cignarelli, Angelo, Perrini, Sebastio, Laviola, Luigi, Giorgino, Francesco, and Natalicchio, Annalisa

Subjects
DIABETIC neuropathies, DIABETES complications, DIABETIC nephropathies, PERIPHERAL vascular diseases, LIFE expectancy, METABOLIC disorders, RETROLENTAL fibroplasia
Abstract

Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Deregulation of autophagy under hyperglycemic conditions is dependent on increased lysine 63 ubiquitination: a candidate mechanism in the progression of diabetic nephropathy

Author

Pontrelli, Paola, Oranger, Annarita, Barozzino, Mariagrazia, Divella, Chiara, Conserva, Francesca, Fiore, Maria Grazia, Rossi, Roberta, Papale, Massimo, Castellano, Giuseppe, Simone, Simona, Laviola, Luigi, Giorgino, Francesco, Piscitelli, Domenico, Gallone, Anna, and Gesualdo, Loreto

Published
2018
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11. The p66Shc Protein Mediates Insulin Resistance and Secretory Dysfunction in Pancreatic β-Cells Under Lipotoxic Conditions

Author

Biondi, Giuseppina, primary, Marrano, Nicola, additional, Dipaola, Lucia, additional, Borrelli, Anna, additional, Rella, Martina, additional, D’Oria, Rossella, additional, Genchi, Valentina A., additional, Caccioppoli, Cristina, additional, Porreca, Immacolata, additional, Cignarelli, Angelo, additional, Perrini, Sebastio, additional, Marchetti, Piero, additional, Vincenti, Leonardo, additional, Laviola, Luigi, additional, Giorgino, Francesco, additional, and Natalicchio, Annalisa, additional

Published
2022
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14. 1414-P: Dapagliflozin Protects Human Cardiac Progenitor Cells from Deleterious Effects of the Secretome from Visceral Adipose Cells of Obese Subjects

Author

PALMA, GIUSEPPE, primary, CACCIOPPOLI, CRISTINA, additional, DORIA, ROSSELLA, additional, GENCHI, VALENTINA ANNAMARIA, additional, SANTARPINO, GIUSEPPE, additional, CIGNARELLI, ANGELO, additional, NATALICCHIO, ANNALISA, additional, LAVIOLA, LUIGI, additional, PEZZOLLA, ANGELA, additional, GIORGINO, FRANCESCO, additional, and PERRINI, SEBASTIO, additional

Published
2022
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15. 441-P: Oleate Prevents Palmitate-Induced Abnormalities in Insulin Signaling in Human Cardiac Progenitor Cells by Inhibiting p38 MAPK and c-Jun Phosphorylation

Author

DORIA, ROSSELLA, primary, CALDERONI, ISABELLA, additional, CACCIOPPOLI, CRISTINA, additional, GENCHI, VALENTINA ANNAMARIA, additional, SANTARPINO, GIUSEPPE, additional, LEONARDINI, ANNA, additional, NATALICCHIO, ANNALISA, additional, PERRINI, SEBASTIO, additional, CIGNARELLI, ANGELO, additional, GIORGINO, FRANCESCO, additional, and LAVIOLA, LUIGI, additional

Published
2022
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18. Mini Review: Effect of GLP-1 Receptor Agonists and SGLT-2 Inhibitors on the Growth Hormone/IGF Axis

Author

Cignarelli, Angelo, primary, Genchi, Valentina Annamaria, additional, Le Grazie, Giulia, additional, Caruso, Irene, additional, Marrano, Nicola, additional, Biondi, Giuseppina, additional, D’Oria, Rossella, additional, Sorice, Gian Pio, additional, Natalicchio, Annalisa, additional, Perrini, Sebastio, additional, Laviola, Luigi, additional, and Giorgino, Francesco, additional

Published
2022
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22. Body mass index versus surrogate measures of central adiposity as independent predictors of mortality in type 2 diabetes.

Author

Orsi, Emanuela, Solini, Anna, Penno, Giuseppe, Bonora, Enzo, Fondelli, Cecilia, Trevisan, Roberto, Vedovato, Monica, Cavalot, Franco, Lamacchia, Olga, Haxhi, Jonida, Nicolucci, Antonio, Pugliese, Giuseppe, for the Renal Insufficiency And Cardiovascular Events (RIACE) Study Group, Laviola, Luigi, Bollanti, Lucilla, Alessi, Elena, Vitale, Martina, Cirrito, Tiziana, Cavallo-Perin, Paolo, and Gruden, Gabriella

Subjects
BODY mass index, TYPE 2 diabetes, OBESITY, LEAN body mass, CARDIOPULMONARY fitness
Abstract

Background: An "obesity paradox" for mortality has been shown in chronic disorders such as diabetes, and attributed to methodological bias, including the use of body mass index (BMI) for obesity definition. This analysis investigated the independent association of BMI versus surrogate measures of central adiposity with all-cause mortality in individuals with type 2 diabetes. Methods: The Renal Insufficiency And Cardiovascular Events Italian Multicentre Study is a prospective cohort study that enrolled 15,773 patients in 19 Italian centres in 2006–2008. Exposures were BMI and the surrogate measures of central adiposity waist circumference (WC), waist-to-height ratio (WHtR), and A Body Shape Index (ABSI). Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%), Results: Age- and sex-adjusted hazard ratios and 95% confidence intervals were significantly higher in BMI-based underweight (1.729 [1.193–2.505), P = 0.004), moderately obese (1.214 [1.058–1.392), P = 0.006) and severely obese (1.703 [1.402–2.068), P < 0.0001), lower in overweight (0.842 [0.775–0.915), P < 0.0001) and similar in mildly obese (0.950 [0.864–1.045), P = 0.292), compared to normal-weight individuals. When further adjusting for smoking, physical activity (PA), and comorbidities, risk was lower also in mildly obese versus normal-weight patients. The BMI-mortality relationship did not change after sequentially excluding ever smokers, individuals with comorbidities, and those died within two years from enrollment and when analyzing separately participants below and above the median age. Conversely, a paradox relationship was observed among inactive/moderately inactive, but not moderately/highly active patients. Mortality risk adjusted for age, gender, smoking, PA and comorbidities was significantly higher in the highest tertile of WC (1.279 [1.089–1.501], P = 0.003), WHtR (1.372 [1.165–1.615], P < 0.0001), and ABSI (1.263 [1.067–1.495], P = 0.007) versus the lowest tertile. However, risk was lower in the intermediate versus lowest tertile for WC (0.823 [0.693–0.979], P = 0.028), similar for WHtR, and higher, though not significantly, for ABSI. Conclusions: An "overweight paradox" remained after controlling for age, smoking, and comorbidities, arguing against a collider bias or reverse causation. However, it could be partly explained by confounding from PA level, possibly through its impact on lean mass and cardiorespiratory fitness. No obesity paradox was observed with WHtR and especially ABSI, which predicted mortality risk associated with central adiposity better than WC. Trial registration ClinicalTrials.gov, NCT00715481, 15 July, 2008 [ABSTRACT FROM AUTHOR]

Published
2022
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23. Impact of Dysfunctional Adipose Tissue Depots on the Cardiovascular System.

Author

D'Oria, Rossella, Genchi, Valentina Annamaria, Caccioppoli, Cristina, Calderoni, Isabella, Marrano, Nicola, Biondi, Giuseppina, Borrelli, Anna, Di Gioia, Ludovico, Giorgino, Francesco, and Laviola, Luigi

Subjects
ADIPOSE tissues, CARDIOVASCULAR system, REACTIVE oxygen species, MESENTERY, CARDIOVASCULAR diseases risk factors, CARDIOVASCULAR diseases, FAT
Abstract

Obesity with its associated complications represents a social, economic and health problem of utmost importance worldwide. Specifically, obese patients carry a significantly higher risk of developing cardiovascular disease compared to nonobese individuals. Multiple molecular mechanisms contribute to the impaired biological activity of the distinct adipose tissue depots in obesity, including secretion of proinflammatory mediators and reactive oxygen species, ultimately leading to an unfavorable impact on the cardiovascular system. This review summarizes data relating to the contribution of the main adipose tissue depots, including both remote (i.e., intra-abdominal, hepatic, skeletal, pancreatic, renal, and mesenteric adipose fat), and cardiac (i.e., the epicardial fat) adipose locations, on the cardiovascular system. Finally, we discuss both pharmacological and non-pharmacological strategies aimed at reducing cardiovascular risk through acting on adipose tissues, with particular attention to the epicardial fat. [ABSTRACT FROM AUTHOR]

Published
2022
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26. Role of Glucose-Lowering Medications in Erectile Dysfunction

Author

Cignarelli, Angelo, primary, Genchi, Valentina Annamaria, additional, D’Oria, Rossella, additional, Giordano, Fiorella, additional, Caruso, Irene, additional, Perrini, Sebastio, additional, Natalicchio, Annalisa, additional, Laviola, Luigi, additional, and Giorgino, Francesco, additional

Published
2021
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27. 1223-P: Effects of Bariatric Surgery on Quality of Life, Body Image, and Sex Life in Obese Women

Author

DI GIOIA, LUDOVICO, primary, PERRINI, SEBASTIO, additional, BRAUN, ANTONIO, additional, ROSSI, ERICA, additional, GIORDANO, FIORELLA, additional, GUARINI, FRANCESCA, additional, SICILIANO, EDOARDO, additional, CIGNARELLI, ANGELO, additional, LEONARDINI, ANNA, additional, NATALICCHIO, ANNALISA, additional, LAVIOLA, LUIGI, additional, BERTOLINO, ALESSANDRO, additional, and GIORGINO, FRANCESCO, additional

Published
2021
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28. 241-OR: Effects of Antidiabetes Therapies on Irisin Levels in Type 2 Diabetes Patients

Author

NATALICCHIO, ANNALISA, primary, MARRANO, NICOLA, additional, BIONDI, GIUSEPPINA, additional, MONTEDORO, ANNA, additional, GRAZIE, GIULIA LE, additional, GIOIA, LUDOVICO DI, additional, GUARINI, FRANCESCA, additional, BORRELLI, ANNA, additional, CIGNARELLI, ANGELO, additional, PERRINI, SEBASTIO, additional, LAVIOLA, LUIGI, additional, and GIORGINO, FRANCESCO, additional

Published
2021
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33. The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor

Author

D’Oria, Rossella, Schipani, Rossella, Leonardini, Anna, Natalicchio, Annalisa, Perrini, Sebastio, Cignarelli, Angelo, Laviola, Luigi, and Giorgino, Francesco

Subjects
Article Subject
Abstract

Reactive oxygen species (ROS) are highly reactive chemical species containing oxygen, controlled by both enzymatic and nonenzymatic antioxidant defense systems. In the heart, ROS play an important role in cell homeostasis, by modulating cell proliferation, differentiation, and excitation-contraction coupling. Oxidative stress occurs when ROS production exceeds the buffering capacity of the antioxidant defense systems, leading to cellular and molecular abnormalities, ultimately resulting in cardiac dysfunction. In this review, we will discuss the physiological sources of ROS in the heart, the mechanisms of oxidative stress-related myocardial injury, and the implications of experimental studies and clinical trials with antioxidant therapies in cardiovascular diseases.

Published
2020
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35. variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

Author

Penno, Giuseppe, Solini, Anna, Bonora, Enzo, Fondelli, Cecilia, Orsi, Emanuela, Zerbini, Gianpaolo, Morano, Susanna, Cavalot, Franco, Lamacchia, Olga, Laviola, Luigi, Nicolucci, Antonio, and Pugliese, Giuseppe

Subjects
Diabetic retinopathy -- Complications and side effects -- Research -- Care and treatment, Chronic kidney failure -- Complications and side effects -- Research -- Care and treatment, Type 2 diabetes -- Complications and side effects -- Research -- Care and treatment, Health
Abstract

OBJECTIVE--To examine the association of hemoglobin (Hb) [A.sub.1c] variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) [...]

Published
2013
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38. Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes: a prospective cohort study

Author

Penno, Giuseppe, primary, Orsi, Emanuela, additional, Solini, Anna, additional, Bonora, Enzo, additional, Fondelli, Cecilia, additional, Trevisan, Roberto, additional, Vedovato, Monica, additional, Cavalot, Franco, additional, Gruden, Gabriella, additional, Laviola, Luigi, additional, Nicolucci, Antonio, additional, and Pugliese, Giuseppe, additional

Published
2020
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41. 1134-P: The Secretome of Visceral Adipose Cells Induces Apoptosis of Cardiac Progenitor Cells in Human Obesity: Protective Effects of the SGLT2 Inhibitor Dapagliflozin

Author

PORRO, STEFANIA, primary, PERRINI, SEBASTIO, additional, CACCIOPPOLI, CRISTINA, additional, DORIA, ROSSELLA, additional, GENCHI, VALENTINA ANNAMARIA, additional, SCHIPANI, ROSSELLA, additional, CIGNARELLI, ANGELO, additional, NATALICCHIO, ANNALISA, additional, LAVIOLA, LUIGI, additional, and GIORGINO, FRANCESCO, additional

Published
2020
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42. 410-P: Effects of Palmitate and Oleate on Apoptosis, Autophagy, Stress, Kinase Phosphorylation, and Enzymes of Fatty Acid Oxidation in Human Cardiac Progenitor Cells from Control and Diabetic Subjects

Author

LAVIOLA, LUIGI, primary, SCHIPANI, ROSSELLA, additional, DORIA, ROSSELLA, additional, CACCIOPPOLI, CRISTINA, additional, LEONARDINI, ANNA, additional, NATALICCHIO, ANNALISA, additional, PERRINI, SEBASTIO, additional, CIGNARELLI, ANGELO, additional, and GIORGINO, FRANCESCO, additional

Published
2020
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46. Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes: a prospective cohort study.

Author

Penno, Giuseppe, Solini, Anna, Orsi, Emanuela, Bonora, Enzo, Fondelli, Cecilia, Trevisan, Roberto, Vedovato, Monica, Cavalot, Franco, Zerbini, Gianpaolo, Lamacchia, Olga, Nicolucci, Antonio, Pugliese, Giuseppe, Laviola, Luigi, and Renal Insufficiency And Cardiovascular Events (RIACE) Study Group

Abstract

Background: It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study.Methods: This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006-2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35 mg/kg/min) to T3 (≤ 4.14 mg/kg/min, highest IR).Results: CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p < 0.0001, and hazard ratio [HR] adjusted for multiple confounders including DKD, 1.140 [95% confidence interval [CI], 1.049-1.238], p = 0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072-1.375], p = 0.002) and in those with nonalbuminuric DKD (1.276 [1.034-1.575], p = 0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and in younger individuals and was observed in those without but not with prior CVD, though interaction was significant only for age.Conclusions: The proxy of insulin sensitivity eGDR predicts all-cause mortality in type 2 diabetes, independent of confounders including DKD. However, the impact of IR in individuals with albuminuric DKD may be mediated by its relationship with albuminuria.Trial Registration: ClinicalTrials.gov , NCT00715481, retrospectively registered 15 July 2008. [ABSTRACT FROM AUTHOR]

Published
2021
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48. Erratum to: The p66Shc redox adaptor protein is induced by saturated fatty acids and mediates lipotoxicity-induced apoptosis in pancreatic beta cells

Author

Natalicchio, Annalisa, Tortosa, Federica, Labarbuta, Rossella, Biondi, Giuseppina, Marrano, Nicola, Carchia, Emanuele, Leonardini, Anna, Cignarelli, Angelo, Bugliani, Marco, Marchetti, Piero, Fadini, Gian Paolo, Giorgio, Marco, Avogaro, Angelo, Perrini, Sebastio, Laviola, Luigi, and Giorgino, Francesco

Published
2015
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