Institutes
Cardiodiabetes and core Lab
Research activity is focused on type 2 diabetes mellitus and cardiovascular diseases. Diabetic patients have an increased incidence of coronary disease and myocardial infarction compared with non-diabetic patients with a similar risk profile. Type 2 diabetes and cardiovascular diseases could be considered different aspects of the same syndrome: i.e. the metabolic syndrome. Metabolic syndrome is a cluster of metabolic abnormalities which includes obesity, insulin resistance, dyslipidemia, hypertension, endothelial dysfunction. Endothelial dysfunction, which represents a common trait of the type 2 diabetes and cardiovascular diseases, is characterized by a reduction of the bioavailability of vasodilators, mainly nitric oxide, which causes an impairment of endothelium-dependent vasodilation. Endothelium-derived nitric oxide is a potent endogenous vasodilator that plays a major role in vascular tone; it is synthesized by endothelial nitric oxide synthase in a multistep reaction from L-arginine. Genetic variants on eNOS gene are associated to type 2 diabetes, cardiovascular diseases and metabolic syndrome.
The group recently demonstrated that these variants produce alternative splicing causing the generation of a novel isoform of eNOS protein, truncated in the C-terminal region and with an altered function. In particular, a significant decrease of insulin sensitivity and endothelial progenitor cells (EPCs), and an increase in proatherogenic markers (ADMA) have been found in subjects carrying this alternative splicing.
The aim is to understand the potential role of the novel eNOS isoform on the development of type 2 diabetes and cardiovascular diseases. In addition, this Unit is evaluating the molecular mechanisms of the precursor of nitric oxide, L-arginine, on alterations of eNOS enzyme activity linked to genetic variants and, eventually, the role of the truncated protein in endothelial cells. The results achieved seems to demonstrate that L-Arginine supplementation is able to overcome the negative effects generated by a genetic modification on vascular function: it induces induce a positive metabolic memory capable of delaying the onset of diabetes mellitus. Moreover, the presence of a greater number of progenitor endothelial cells, the reduction in markers of oxidative stress also seems to indicate the presence of a vascular memory.
As vascular memory can affect the metabolic memory will be the aim of future in vitro and in vivo studies in human endothelial cell line and in progenitor cells. In particular Cardiodiabetes and core Lab is studying the potential legacy effects of L-arginine on metabolic and vascular metabolism, analyzing the profiles of gene and protein expression and evaluating the metabolism of glucose and lipid metabolism and mitochondrial function.
Another field in which the group is particularly involved is the prevention type 2 diabetes. In particular, it has been shown that the presence of the polymorphism of eNOS increased significantly the risk of alteration of glucose metabolism and to develop type 2 diabetes compared to non-carriers of the polymorphism in a large cohort of individuals at high risk for developing diabetes.
The Cardiodiabetes and core Lab laboratory is also involved in sample handling for Clinical Trials mainly related to innovative treatment of type 1 and 2 diabetes mellitus, cardiovascular diseases and over the years it has specialized in assays for diseases related to metabolism, cardiovascular disease, inflammation and atherosclerosis.
As vascular memory can affect the metabolic memory will be the aim of future in vitro and in vivo studies in human endothelial cell line and in progenitor cells. In particular Cardiodiabetes and core Lab is studying the potential legacy effects of L-arginine on metabolic and vascular metabolism, analyzing the profiles of gene and protein expression and evaluating the metabolism of glucose and lipid metabolism and mitochondrial function.
Another field in which the group is particularly involved is the prevention type 2 diabetes. In particular, it has been shown that the presence of the polymorphism of eNOS increased significantly the risk of alteration of glucose metabolism and to develop type 2 diabetes compared to non-carriers of the polymorphism in a large cohort of individuals at high risk for developing diabetes.
The Cardiodiabetes and core Lab laboratory is also involved in sample handling for Clinical Trials mainly related to innovative treatment of type 1 and 2 diabetes mellitus, cardiovascular diseases and over the years it has specialized in assays for diseases related to metabolism, cardiovascular disease, inflammation and atherosclerosis.
Galluccio E, Cassina L, Russo I, Gelmini F, Setola E, Rampoldi L, Citterio L, Rossodivita A, Kamami M, Colombo A, Alfieri O, Carini M, Bosi E, Trovati M, Piatti P, Monti LD, Casari G. A novel truncated form of eNOS associates with altered vascular function. Cardiovasc Res. 2014 Mar 1;101(3):492-502.
Baldi S, Bonnet F, Laville M, Morgantini C, Monti L, Hojlund K, Ferrannini E, Natali A; Risc investigators (Monti LD). Influence of apolipoproteins on the association between lipids and insulin sensitivity: a cross-sectional analysis of the RISC Study. Diabetes Care. 2013 Dec;36(12):4125-31.
Kozakova M, Natali A, Dekker J, Beck-Nielsen H, Laakso M, Nilsson P, Balkau B, Ferrannini E; Risc Investigators (Monti LD.). Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study. Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1409-17.
Dei Cas A, Spigoni V, Franzini L, Preti M, Ardigò D, Derlindati E, Metra M, Monti LD, Dell’Era P, Gnudi L, Zavaroni I. Lower endothelial progenitor cell number, family history of cardiovascular disease and reduced HDL-cholesterol levels are associated with shorter leukocyte telomere length in healthy young adults. Nutr Metab Cardiovasc Dis. 2013 Mar;23(3):272-8.
Monti LD, Casiraghi Mc, Setola E, Galluccio E, Pagani MA, Quaglia L, Bosi E, Piatti PM. L-Arginine enriched biscuits improve endothelial function and glucose metabolism: A pilot study in healthy subjects and a cross-over study in subjects with impaired glucose tolerance and metabolic syndrome. Metabolism. 2013 Feb;62(2):255-64.
Piatti PM, Marone E, Mantero M, Setola E, Galluccio E, Lucotti P, Shehaj E, Villa V, Perticone F, Venturini M, Palini A, Airoldi F, Faglia E, Del Maschio A, Colombo A, Chiesa R, Bosi E, Monti LD. Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial. Acta Diabetol. 2013 Jun;50(3):373-82.
Monti LD, Lucotti PC, Setola E, Rossodivita A, Pala MG, Galluccio E, Lacanna G, Castiglioni A, Cannoletta M, Meloni C, Zavaroni I, Bosi E, Alfieri O, Piatti PM. Effects of chronic elevation of atrial natriuretic peptide and free fatty acid levels in the induction of type 2 diabetes mellitus and insulin resistance in patients with mitral valve disease. Nutr Metab Cardiovasc Dis. 2012 Jan;22(1):58-65.
Monti LD, Setola E, Lucotti PC, Marrocco-Trischitta MM, Comola M, Galluccio E, Poggi A, Mammì S, Catapano Al, Comi G, Chiesa R, Bosi E, Piatti PM. Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2012 Oct;14(10):893-900.
Handberg A, Højlund K, Gastaldelli A, Flyvbjerg A, Dekker Jm, Petrie J, Piatti P, Beck-Nielsen H; Risc Investigators (Monti LD). Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population. J Intern Med. 2012 Mar;271(3):294-304.
Bobbioni-Harsch E, Pataky Z, Makoundou V, Laville M, Disse E, Anderwald C, Konrad T, Golay A; Risc Investigators (Monti LD). From metabolic normality to cardiometabolic risk factors in subjects with obesity. Obesity. 2012. 20:2063-9.