title: The good and the bad in the link between insulin resistance and vascular calcification.
abstract: Medial arterial calcification is a common finding in subjects with diabetes mellitus. In vitro, glucose or insulin supplementations promote a phenotypic shift of smooth muscle cells into osteogenic cells, but the mechanisms driving this conversion are poorly understood. The binomial hyperglycaemia/hyperinsulinemia is typical of insulin resistance states, in which the metabolic and vasomotor ("good") actions of insulin are selectively impaired, whereas its mitogenic ("bad") signals are potently enhanced. Under these conditions, insulin can exert pro-atherosclerotic effects and promote vascular calcification. In this setting, the metabolic and mitogenic pathways may be not entirely antagonist, because they interact to traduce the normal insulin signal into inhibition of calcification. Emerging data suggest that the two pathways may converge on the regulation of phosphate transport and extracellular inorganic phosphate (Pi) concentrations. Two antagonist enzymes governing Pi metabolism are alkaline phosphatase (ALP) and the ectonucleotide pyrophosphatase/phosphodiesterase-1 (also known as PC-1): while ALP is up-regulated in calcified diabetic arteries, PC-1 is also implicated in the genesis of insulin resistance. Therefore, we suggest that the functional interactions between ALP and PC-1 may link insulin resistance to vascular calcification.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova, Medical School, Padova, Italy. gianpaolofadini@hotmail.com
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.forename: Paolo
authors.initials: P
authors.lastname: Pauletto
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Marcello
authors.initials: M
authors.lastname: Rattazzi
mesh_terms: D000469:Alkaline Phosphatase; D002114:Calcinosis / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D014652:Vascular Diseases
chemical_list: D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases