A5008864986- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Genetics and Neurodevelopmental Disorders
- Diabetes Treatment and Management
- Diet and metabolism studies
- Obesity, Physical Activity, Diet
- Endoplasmic Reticulum Stress and Disease
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Adipose Tissue and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Congenital heart defects research
- Birth, Development, and Health
- Carbohydrate Chemistry and Synthesis
- Metabolism and Genetic Disorders
- Cardiac Ischemia and Reperfusion
- Genomics and Rare Diseases
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Pluripotent Stem Cells Research
Bambino Gesù Children's Hospital
2016-2025
University of Rome Tor Vergata
2015-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2023
Diabetes Australia
2008-2023
University of Virginia
2021
Fatebenefratelli Hospital
2018
University of Turin
2016
Toscana Biomarkers (Italy)
2008-2014
Catholic University of America
2012
University of Florence
2007-2010
Diabetes mellitus is a heterogeneous disorder that can occur at any age.1 Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, rare usually associated with intrauterine growth retardation.2 Like in general, neonatal and be either transient or permanent. Transient abnormalities chromosome 6,2,3 whereas mutations insulin promoter factor 1 result pancreatic agenesis permanent diabetes.4 We describe two patients whom complete deficiency...
<h3>Background</h3> Histone deimination regulates gene function and contributes to antimicrobial response, allowing the formation of neutrophil extracellular traps (NETs). Deiminated proteins are target anti-citrullinated peptides antibodies (ACPA) in rheumatoid arthritis (RA). <h3>Objective</h3> The objective this paper is test hypothesis that RA sera react with deiminated histones contained NETs. <h3>Methods</h3> Neutrophils from peripheral blood were stimulated A23187 acid treated;...
Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented Italy, genetic cause remains unknown. Because Akita mouse bearing mutation Ins2 gene exhibits PNDM associated with pancreatic β cell apoptosis, we sequenced human insulin subjects unidentified mutations. We discovered 7 heterozygous mutations 10 unrelated probands. In 8 these patients,...
KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term unclear. Sulfonylurea failure seen about 44% people type 2 after 5 years treatment. Therefore, we did a 10-year multicentre follow-up study large international cohort address key questions relating...
Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as with onset within 6 weeks from birth that requires insulin therapy for at least 2 weeks, were considered exceedingly rare conditions, a global incidence of 1:500,000–1:400,000 live births. The new definition NDM recently adopted, includes patients months age, has prompted studies have set the form alone between 1:210,000 1:260,000 Aim present work was to ascertain (i.e. + form) in Italy years 2005–2010....
An etiologic diagnosis of diabetes can affect the therapeutic strategy and prognosis chronic complications. The aim present study was to establish relative percentage different subtypes in patients attending Italian pediatric centers influence an on therapy. This a retrospective study. clinical records 3781 consecutive (age, 0 18 years) referred 15 clinics with or impaired fasting glucose from January 1, 2007 December 31, 2012 were examined. characteristics at their first referral centers,...
In this study, a second case of hyperinsulinemic hypoglycemia due to activation glucokinase is reported. The 14-year-old proband had history neonatal hypoglycemia, treated with diazoxide. He was admitted coma and convulsions nonketotic hypoglycemia. His BMI 34 kg/m2, his fasting blood glucose ranged from 2.1 2.7 mmol/l, associated inappropriately high serum levels insulin, C-peptide, proinsulin. An oral tolerance test (OGTT) showed exaggerated responses these peptides followed by profound...
Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic etiology unknown in most PNDM patients. Recently, heterozygous activating mutations KCNJ11, encoding Kir6.2, pore forming subunit ATP-dependent potassium (KATP) channel pancreatic β-cell, were found patients with PNDM. Closure KATP exerts pivotal role secretion...
Recently, a syndrome of Mutant INS-gene-induced Diabetes Youth (MIDY, derived from one 26 distinct mutations) has been identified as cause insulin-deficient diabetes, resulting expression misfolded mutant proinsulin protein in the endoplasmic reticulum (ER) insulin-producing pancreatic beta cells. Genetic deletion one, two, or even three alleles encoding insulin mice does not necessarily lead to diabetes. Yet MIDY patients are INS-gene heterozygotes; inheritance allele, causes Although...
To investigate the prevalence of maturity-onset diabetes young (MODY) in Italian children with incidental hyperglycemia.Among 748 subjects age 1-18 years hyperglycemia, minimal diagnostic criteria for MODY were met by 172 families. Mutational analyses glucokinase (GCK) and hepatocyte nuclear factor 1alpha (HNF1A) genes performed.We identified 85 GCK gene mutations 109 probands 10 HNF1A 12 probands. In patients, median neonatal weight at first evaluation lower than those found patients...
Mutations in the Kir6.2 subunit (KCNJ11) of ATP-sensitive potassium channel (KATP) underlie neonatal diabetes mellitus. In severe cases, mutations developmental delay, epilepsy, and (DEND). All examined decrease ATP inhibition KATP, which is predicted to suppress electrical activity neurons (peripheral central), muscle, pancreas. Inhibitory sulfonylureas (SUs) have been used successfully treat patients with activating mutations. There are two reports improved neurological features SU-treated...
Permanent neonatal diabetes mellitus (PNDM) can be caused by insulin mutations. We generated induced pluripotent stem cells from fibroblasts of a patient with PNDM and undetectable at birth due to homozygous mutation in the translation start site gene. Differentiation mutant resulted insulin-negative endocrine expressing MAFA, NKX6.1, chromogranin A. Correction differentiation pancreatic restored production secretion levels comparable those wild-type cells. Grafting corrected into mice,...
Transglutaminase 2 (TGase 2) is a Ca+2-dependent enzyme that catalyzes both intracellular and extracellular cross-linking reactions by transamidation of specific glutamine residues. TGase known to be involved in the membrane-mediated events required for glucose-stimulated insulin release from pancreatic beta cells. Here we show targeted disruption impairs secretion. 2-/- mice glucose intolerance after intraperitoneal loading. manifest tendency develop hypoglycemia administration exogenous as...
Glucokinase (GCK) serves as the pancreatic glucose sensor. Heterozygous inactivating GCK mutations cause hyperglycemia, whereas activating hypoglycemia. We studied V62M mutation identified in two families and co-segregating with hyperglycemia to understand how this resulted reduced function. Structural modeling locates close five naturally occurring allosteric activator site of enzyme. Recombinant glutathionyl S-transferase-V62M is paradoxically activated rather than inactivated due a...
Mutations in the pancreatic ATP-sensitive K(+) channel (K(ATP) channel) cause permanent neonatal diabetes mellitus (PNDM) humans. All of K(ATP) mutations examined result decreased ATP inhibition, which turn is predicted to suppress insulin secretion. Here we describe a patient with severe PNDM, includes developmental delay and epilepsy, addition (developmental delay, [DEND]), due G334D mutation Kir6.2 subunit channel. The was wholly unresponsive sulfonylurea therapy (up 1.14 mg . kg(-1)...