Diabetology and molecular endocrinology

The main focus of the Diabetology and molecolar endcrinology unit at IBCIT is the investigation of the molecular basis of monogenic forms of derangement of glucose metabolism including both monogenic diabetes (MD) and congenital hyperinsulinism (CHI). In the laboratory, a molecular genetic screening program has been established for most of the genes involved in the two main subtypes of monogenic diabetes, i.e. the Maturity Onset Diabetes of the Young (MODY) and Neonatal/Infancy Onset Diabetes (Monogenic Diabetes of Infancy, MDI) and for most of the genes frequently causing CHI. Recent advances in understanding the genetic basis of a subtype of MDI caused by mutations of the insulin gene with proteotoxic effect has opened a new research stream in the lab, focused on the analysis of the molecular mechanism(s) involved in the pancreatic beta cell apoptosis linked to endoplasmic reticulum stress. Finally, the metabolic and genetic determinants of the progression from the state of impaired glucose tolerance (IGT) to diabetes in obese Italian children/adolescents are also subject of intense investigation.

Unit members

Selected publications

Bonfanti R, Colombo C, Nocerino V, Massa O, Iafusco D, Viscardi M, Chiumello G, Meschi F, Barbetti F. Insulin gene mutations as cause of diabetes in children negative for five type 1 diabetes autoantibodies. Diabetes Care. published on line 2008 Oct 7, PMID 18840

Colombo C, Porzio O, Massa O, Vasta M, Salardi S, Beccaria L, Liu M, Arvan P, Monciotti C, Toni S, Pedersen O, Hansen T, Federici L, Pesavento R, Cadario F, Federici G, Ghirri P, Iafusco D, Barbetti F and the. Early onset diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (SIEDP). (2008) Seven mutations in the human insulin gene linked to permanent neonatal/infancy onset diabetes mellitus. J Clin Invest 118:2148-2156

Porzio O, Massa O, Cunsolo V, Colombo C, Malaponti M, Bertuzzi F, Hansen T , Johansen A, Pedersen O, Meschi F, Terrinoni A, Melino G, Federici M, Decarlo N, Menicagli M, Campani D, Marchetti P, Ferdaoussi M, Froguel P, Federici G, Vaxillaire M, Barbetti F. (2007) Missense Mutations in TGM2 Gene encoding transglutaminase 2 are associated with familial type 2 diabetes. Hum Mutat 28:1150

Masia R, Koster JC, Tumini S, Chiarelli F, Colombo C, Nichols CG, Barbetti F. (2007) An ATP-binding mutation (G334D) in KCNJ11 is associated with a sulfonylurea-insensitive form of DEND (Developmental Delay, Epilepsy, and Neonatal Diabetes). Diabetes 56.328-336

Tonini G, Bizzarri C, Bonfanti R, Vanelli M, Cerutti F, Faleschini E, Meschi F, Prisco F, Ciacco E, Cappa M, Torelli C, Cauvin V, Tumini S, Iafusco D, Barbetti F and the Early Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. (2006) Sulphonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 gene. Diabetologia 49:2210-2213