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.