Abstract
Insulin analogues provide clinically important benefits for people with diabetes,
including more predictable action profiles and lower risk of hypoglycemia compared
with human insulin. However, it has been suggested that certain insulin analogues
may lead to greater activation of insulin-like growth factor-1 (IGF-1) signaling,
with risk for adverse mitogenic effects. This article aims to critically review studies
on the mitogenic effects of the insulin analogue insulin glargine (glargine) and its
metabolites. A review of in vitro studies suggests that glargine may stimulate mitogenic
activity in some cell lines at supraphysiological concentrations (nanomolar/micromolar
concentrations). Mitogenicity appeared to be related to the expression of the IGF-1
receptor, being present in cells expressing high levels of the receptor and absent
in cells with limited or no IGF-1 receptor expression. In animal studies, glargine
did not promote tumor growth, despite administration at supraphysiological concentrations
(nanomolar/micromolar), which are unlikely to be observed in clinical practice because
the doses needed to produce these concentrations are liable to lead to hypoglycemia.
Furthermore, glargine in vivo is rapidly transformed into its metabolites, the metabolic
and mitogenic characteristics of which have been shown to be broadly equal to those
of human insulin. Thus, the suggestion of increased relative mitogenic potency of
insulin glargine seen in some cell lines does not appear to carry over to the in vivo
situation in animals and humans.
Key words
insulin - insulin analogues - insulin-like growth factor-1 - mitogenicity
References
Correspondence
tciaraldi@ucsd.edu
