Horm Metab Res 2011; 43(1): 1-10
DOI: 10.1055/s-0030-1267203

© Georg Thieme Verlag KG Stuttgart · New York

Review on the In Vitro Interaction of Insulin Glargine with the Insulin/Insulin-like Growth Factor System: Potential Implications for Metabolic and Mitogenic Activities

T. P. Ciaraldi1 , T. Sasaoka2
  • 1VA San Diego Healthcare System and University of California, San Diego, La Jolla, CA, USA
  • 2Department of Clinical Pharmacology, University of Toyama, Toyama, Japan
Further Information

Publication History

received 30.06.2010

accepted 14.09.2010

Publication Date:
11 October 2010 (online)


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.



T. P. Ciaraldi, PhD 

Department of Medicine (9111G)

University of California

San Diego

9500 Gillman Drive

La Jolla

CA 92093


Phone: +1/858/552 8585 ext. 6450

Fax: +1/858/642 6242

Email: tciaraldi@ucsd.edu