A5047997260- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
- Diabetes Treatment and Management
- Genetic Associations and Epidemiology
- Diabetes and associated disorders
- Cardiovascular Function and Risk Factors
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Genomics and Rare Diseases
- Folate and B Vitamins Research
- Diet and metabolism studies
- Diet, Metabolism, and Disease
- Helicobacter pylori-related gastroenterology studies
- Metabolism and Genetic Disorders
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Cytokine Signaling Pathways and Interactions
- Chronic Kidney Disease and Diabetes
- Metabolomics and Mass Spectrometry Studies
- Nitric Oxide and Endothelin Effects
- Bioinformatics and Genomic Networks
Casa Sollievo della Sofferenza
2015-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2024
University of Foggia
2020
Nuovo Ospedale San Giovanni di Dio
2007-2018
University of Chieti-Pescara
2008
Sapienza University of Rome
1994-2007
The University of Texas Southwestern Medical Center
2007
University of Pisa
2007
Transcription factors operate in developmental processes to mediate inductive events and cell competence, perturbation of their function or regulation can dramatically affect morphogenesis, organogenesis, growth. We report that a narrow spectrum amino-acid substitutions within the transactivation domain v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF), leucine zipper-containing transcription factor AP1 superfamily, profoundly development. Seven different de novo missense...
Insulin resistance (IR) is pathogenic for type 2 diabetes and coronary artery disease (CAD). The K121Q polymorphism of the ENPP1/PC-1 gene associated with IR. Our aim was to investigate role 121Q variant on risk CAD. Nondiabetic control subjects (n = 638), diabetic patients without CAD 535), 434) from Italy U.S. were studied. proportion carriers progressively increased in three groups (27.4, 28.8, 33.2%, respectively; adjusted P value 0.027). Among 969), had an developing before age 65 years...
Aquaporin 7 (AQP7), the gateway protein controlling glycerol release, has recently emerged as a modulator of adipocyte metabolism. AQP7 knockout mice develop obesity and hyperglycemia. The contribution to these abnormalities in humans is unknown. We examined whether common single nucleotide polymorphisms (SNPs) gene modulate risk related abnormalities. Among several SNPs we identified, A-953G promoter was associated with type 2 diabetes 977 (530 female/447 male) Caucasians: odds ratio for XG...
Background High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have reported, so far, type 2 diabetes. We studied role on coronary artery disease, major events all-cause mortality Methods tested association circulating concentrations (cardiovascular death, non-fatal myocardial infarction stroke) 2,313 diabetic patients European ancestry from two cross-sectional...
Insulin resistance plays a major role in dyslipidemia, cardiovascular disease, and type 2 diabetes. TRB3, mammalian tribbles homolog, whose chromosomal region 20p13-p12 has been linked to human diabetes, impairs insulin signaling through the inhibition of Akt phosphorylation is overexpressed murine models resistance. We here report that prevalent TRB3 missense Q84R polymorphism significantly (P < 0.05) associated with several resistance–related abnormalities two independent cohorts (n...
Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved bone calcification processes, both which compromised diabetes. We aimed to evaluate possible associations osteocalcin, with cardiovascular (CVD) diabetic retinopathy (DR) among people type 2 (T2D).Osteocalcin, concentrations were measured at enrolment 848 participants T2D from the Sapienza University Mortality Morbidity Event...
Uncoupling protein-2 (UCP2) regulates insulin secretion and may play an important role in linking obesity to type 2 diabetes (T2D). Previous studies of the UCP2 promoter −866G/A single nucleotide polymorphisms (SNP) T2D have given opposite results. We tested distribution SNP 746 patients 327 healthy unrelated Caucasians from Italy. also for effect P12A variant peroxisomal proliferator-activated receptor-γ2 (PPARγ2) gene on risk by SNP. Compared with −866G/G carriers, a progressively reduced...
Context: The prevalence of type 2 diabetes (T2D), particularly among young adults, has been rising steadily during the past decades. T2D, especially in its early-onset subtype, is under genetic control. TRIB3 inhibits insulin-stimulated Akt phosphorylation and subsequent insulin action. A gain-of-function polymorphism, Q84R (rs2295490), impairs signaling. Objective: objective study was to verify association with: 1) either subtyped or not according age at diagnosis (early-onset, <45 yr, ≥ 45...
In the endothelium, insulin promotes nitric oxide (NO) production, through receptor/IRS-1/PI3-Kinase/Akt/eNOS signaling pathway. An inhibitor of action, TRIB3, has recently been identified which affects action by binding to and inhibiting Akt phosphorylation. We have described a Q84R gain-of-function polymorphism TRIB3 with R84 variant being associated resistance an earlier age at myocardial infarction.To investigate impact on endothelial we cultured human umbilical vein cells (HUVECs)...
Signal transduction cascades involving Rho-associated kinases (ROCK), the serine/threonine downstream effectors of Rho, have been implicated in regulation diverse cellular functions including cytoskeletal organization, cell size control, modulation gene expression, differentiation, and transformation. Here we show that ROCK2, predominant ROCK isoform skeletal muscle, is progressively up-regulated during mouse myoblast differentiation highly expressed dermomyotome muscle precursor cells...
Conflicting results have been reported regarding the effect of peroxisome proliferator‐activated receptor‐γ−2 (PPARγ2) Pro12Ala polymorphism, (singly or in combination with silent C1431T polymorphism) on BMI. Gender‐based dimorphism has evidenced for genes that affect BMI, but few and conflicting data are available PPARγ2. We sought to investigate whether interacts gender modulating BMI 566 nondiabetic unrelated white subjects (men:women = 211:355, age 36.59 ± 11.85; 25.36 4.53). In whole...
The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator insulin receptor (IR) activation, plays role on signaling, secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) transfected in HepG2 liver-, L6 skeletal muscle- INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 GSK3-beta Ser9 phosphorylation L6), PEPCK mRNA levels (HepG2)...
The cardiovascular benefits of fibrates have been shown to be heterogeneous and depend on the presence atherogenic dyslipidemia. We investigated whether genetic variability in PPARA gene, coding for pharmacological target (PPAR-α), could used improve selection patients with type 2 diabetes who may derive benefit from addition this treatment statins. identified a common variant at locus (rs6008845, C/T) displaying study-wide significant influence effect fenofibrate major events (MACE) among...
Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on in high-risk individuals.A prospective study (average follow-up, 37 months) was conducted for major events (myocardial infarction [MI], stroke, death) from Gargano Heart Study (GHS; n = 330 with type 2 diabetes coronary artery disease), Tor Vergata Atherosclerosis (TVAS; 141 who had MI), Cardiovascular Risk Extended...
Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, chronic metabolic disorder which imposes tremendous burden to morbidity and mortality worldwide. Unraveling molecular mechanisms underlying resistance would improve setting up preventive treatment strategies diabetes. Down-regulation GALNT2, an UDPN-acetyl-alpha-D-galactosamine polypeptideN-acetylgalactosaminyltransferase-2 (ppGalNAc-T2), causes impaired signaling cultured human liver cells. In addition,...
Single nucleotide polymorphism (SNP) rs10911021 at the glutamate-ammonia ligase (GLUL) locus has been associated with an increased risk of coronary heart disease in individuals type 2 diabetes. The effect this SNP on mortality was investigated among 1,242 white subjects diabetes from Joslin Kidney Study (JKS) (n = 416) and Gargano Mortality (GMS) 826). During a mean follow-up 12.8 ± 5.8 7.5 2.2 years, respectively, total 215 164 deaths were observed two studies. In both cohorts, all-cause...
Branched chain amino acids (BCAA) are essential elements of the human diet, which display increased plasma levels in obesity and regained particular interest as potential biomarkers for development diabetes. To define determinants insulin resistance (IR) we investigated 73 genes involved BCAA metabolism or regulation by fine-scale haplotype mapping two European populations with metabolic syndrome. French Romanians (n = 465) were genotyped SNPs (Affymetrix) enriched imputation (BEAGLE 4.1) at...
ATM (ataxia-telangiectasia mutated) gene plays a central role in the DNA-damage response pathway. We characterized protein expression immortalized cells from AT and AT-variant patients, heterozygotes correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest p53-Ser 15 phosphorylation. On Western blots, full-length was detected eight of 18 cases, albeit at 1–32% normal levels, whereas truncated single case, despite prevalence among cases truncation mutations. Of ataxia...