Abstract

Objective: It was reported that the long acting insulin analogue glargine induces cell proliferation in a human osteosarcoma cell line, and therefore might induce or accelerate tumor growth. Induction of cell proliferation would be particularly relevant for insulin treatment of subjects with diabetes mellitus and the potential of bearing tumor cells, e.g. a history of a malignant disease.

Research Design and Methods: Proliferation, apoptosis and the expression levels of insulin receptor, IGF-I receptor and IRS 2 were analyzed in human pancreatic cancer cells (Colo-357) after incubation (72 hours) with insulin glargine (G) or regular human insulin (RHI) at 0 – 100nM. 125 subjects after partial or total pancreatectomy due to pancreatic carcinoma were analyzed over a median follow-up period of 22 month.

Results: There was no significant difference between G and RHI with respect to regulation of proliferation and apoptosis of Colo-357 cells. The expression levels of insulin receptor, IGF-I receptor and IRS 2 as a downstream molecule of both receptor signalling pathways were not altered at any concentration tested. The insulin receptor was down-regulated to a similar degree by G and RHI at high insulin concentrations (p<0.0001 for G, p=0.002 for RHI). The median survival time after pancreatic surgery was 15 months. Survival analysis showed that the time-dependent proportion of patients surviving was identical in patients receiving insulin glargine versus insulin treatment without glargine and control subjects without diabetes mellitus after surgery (p=0.4, 3-sample comparison).

Conclusion: Regular human insulin and insulin glargine may be used to treat diabetes mellitus in patients with pancreatic cancer.