Proliferation of Colo-357 Pancreatic Carcinoma Cells and Survival of Patients With Pancreatic Carcinoma Are Not Altered by Insulin Glargine

  1. Saskia Erbel, PHD1,
  2. Christina Reers, PHD1,
  3. Volker W. Eckstein, PHD2,
  4. Jörg Kleeff, MD3,
  5. Markus W. Büchler, MD3,
  6. Peter P. Nawroth, MD1 and
  7. Robert A. Ritzel, MD1
  1. 1Department of Internal Medicine I, University of Heidelberg, Heidelberg, Germany
  2. 2Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
  3. 3Department of General Surgery, University of Heidelberg, Heidelberg, Germany
  1. Corresponding author: Robert A. Ritzel, MD, Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. E-mail: robert_ritzel{at}uni-heidelberg.de

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 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 insulin receptor substrate (IRS) 2 were analyzed in human pancreatic cancer cells (Colo-357) after incubation (72 h) with insulin glargine or regular human insulin at 0–100 nmol/l. A total of 125 subjects, after partial or total pancreatectomy due to pancreatic carcinoma, were analyzed over a median follow-up period of 22 months.

RESULTS—There was no significant difference between glargine and regular human insulin with respect to regulation of proliferation and apoptosis of Colo-357 cells. The expression levels of insulin receptor, IGF-I receptor, and IRS2 as a downstream molecule of both receptor signaling pathways were not altered at any concentration tested. The insulin receptor was downregulated to a similar degree by glargine and regular human insulin at high insulin concentrations (P < 0.0001 for glargine, P = 0.002 for regular human insulin). The median survival time after pancreatic surgery was 15 months. Survival analysis showed that the time-dependent proportion of patients who survived was identical in patients receiving insulin glargine versus insulin treatment without glargine and control subjects without diabetes after surgery (P = 0.4, three-sample comparison).

CONCLUSIONS—Regular human insulin and insulin glargine may be used to treat diabetes in patients with pancreatic cancer.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 3 March 2008. DOI: 10.2337/dc07-2015.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted February 20, 2008.
    • Received October 18, 2007.
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  1. Diabetes Care vol. 31 no. 6 1105-1111
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