Insulin is a major regulator of cell metabolism but, in addition, is also a
growth factor.
Insulin effects in target cells are mediated by the
insulin receptor (IR), a transmembrane
protein with enzymatic (
tyrosine kinase) activity. The
insulin receptor, however, is represented by a heterogeneous family of
proteins, including two different IR
isoforms and also hybrid receptors resulting from the IR hemireceptor combination with a hemireceptor of the cognate
IGF-1 receptor. These different receptors may bind
insulin and its analogs with different affinity and produce different biologic effects. Since many years, it is known that many
cancer cells require
insulin for optimal in vitro growth. Recent data indicate that: (1)
insulin stimulates growth mainly via its own receptor and not the
IGF-1 receptor; (2) in many
cancer cells, the IR is overexpressed and the A
isoform, which has a predominant mitogenic effect, is more represented than the B
isoform. These characteristics provide a selective growth advantage to malignant cells when exposed to
insulin. For this reason, all conditions of
hyperinsulinemia, both endogenous (
prediabetes,
metabolic syndrome,
obesity,
type 2 diabetes before pancreas exhaustion and
polycystic ovary syndrome) and exogenous (
type 1 diabetes) will increase the risk of
cancer.
Cancer-related mortality is also increased in patients exposed to
hyperinsulinemia but other factors, related to the different diseases, may also contribute. The complexity of the diseases associated with
hyperinsulinemia and their
therapies does not allow a precise evaluation of the
cancer-promoting effect of
hyperinsulinemia, but its detrimental effect on
cancer incidence and mortality is well documented.