The Links Between Insulin Resistance, Diabetes, and Cancer

Overview

Journal Curr Diab Rep

Publisher Current Science

Specialty Endocrinology

Date 2012 Dec 29

PMID 23271574

Citations 84

Authors

Etan Orgel

Steven D Mittelman

Affiliations

Soon will be listed here.

Abstract

The growing epidemic of obesity has resulted in a large increase in multiple related diseases. Recent evidence has strengthened the proposed synergistic relationship between obesity-related insulin resistance (IR) and/or diabetes mellitus (DM) and cancer. Within the past year, many studies have examined this relationship. Although the precise mechanisms and pathways are uncertain, it is becoming clear that hyperinsulinemia and possibly sustained hyperglycemia are important regulators of not only the development of cancer but also of treatment outcome. Further, clinical decision-making regarding the treatment of choice for DM will likely be impacted as we learn more about the non-metabolic effects of the available hyperglycemic agents. In our review, we endeavored to synthesize the recent literature and provide a concise view of the journey from macro-level clinical associations to specific mechanistic relationships being elucidated in cell lines and animal models.

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References

Bjorge T, Lukanova A, Jonsson H, Tretli S, Ulmer H, Manjer J . Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project. Cancer Epidemiol Biomarkers Prev. 2010; 19(7):1737-45. DOI: 10.1158/1055-9965.EPI-10-0230. View

Stocks T, Borena W, Strohmaier S, Bjorge T, Manjer J, Engeland A . Cohort Profile: The Metabolic syndrome and Cancer project (Me-Can). Int J Epidemiol. 2009; 39(3):660-7. PMC: 2878454. DOI: 10.1093/ije/dyp186. View

Li W, Yuan Y, Qiao M, Zhang Y . High dose glargine alters the expression profiles of microRNAs in pancreatic cancer cells. World J Gastroenterol. 2012; 18(21):2630-9. PMC: 3369999. DOI: 10.3748/wjg.v18.i21.2630. View

Pan J, Chen C, Jin Y, Fuentes-Mattei E, Velazquez-Tores G, Benito J . Differential impact of structurally different anti-diabetic drugs on proliferation and chemosensitivity of acute lymphoblastic leukemia cells. Cell Cycle. 2012; 11(12):2314-26. PMC: 3383592. DOI: 10.4161/cc.20770. View

Johnson J, Bowker S . Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials. Diabetologia. 2010; 54(1):25-31. DOI: 10.1007/s00125-010-1933-3. View

Malaguarnera R, Sacco A, Voci C, Pandini G, Vigneri R, Belfiore A . Proinsulin binds with high affinity the insulin receptor isoform A and predominantly activates the mitogenic pathway. Endocrinology. 2012; 153(5):2152-63. DOI: 10.1210/en.2011-1843. View

Wild S, Roglic G, Green A, Sicree R, King H . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5):1047-53. DOI: 10.2337/diacare.27.5.1047. View

Danaei G, Finucane M, Lu Y, Singh G, Cowan M, Paciorek C . National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet. 2011; 378(9785):31-40. DOI: 10.1016/S0140-6736(11)60679-X. View

Larsson S, Mantzoros C, Wolk A . Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer. 2007; 121(4):856-62. DOI: 10.1002/ijc.22717. View

10.

Ward W, LaCava E, Paquette T, Beard J, Wallum B, Porte Jr D . Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia. 1987; 30(9):698-702. DOI: 10.1007/BF00296991. View

11.

Porter H, Carey G, Keegan A . Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death. Exp Cell Res. 2012; 318(14):1745-58. PMC: 3395425. DOI: 10.1016/j.yexcr.2012.04.020. View

12.

Shao M, Hollar S, Chambliss D, Schmitt J, Emerson R, Chelladurai B . Targeting the insulin growth factor and the vascular endothelial growth factor pathways in ovarian cancer. Mol Cancer Ther. 2012; 11(7):1576-86. PMC: 4497519. DOI: 10.1158/1535-7163.MCT-11-0961. View

13.

Teng J, Hou R, Li D, Yang R, Qin J . Glargine promotes proliferation of breast adenocarcinoma cell line MCF-7 via AKT activation. Horm Metab Res. 2011; 43(8):519-23. DOI: 10.1055/s-0031-1280780. View

14.

Fox E, Miller T, Balko J, Kuba M, Sanchez V, Smith R . A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res. 2011; 71(21):6773-84. PMC: 3206206. DOI: 10.1158/0008-5472.CAN-11-1295. View

15.

Kim J, Kim E, Liu D, Lee J, Solis L, Behrens C . Prognostic impact of insulin receptor expression on survival of patients with nonsmall cell lung cancer. Cancer. 2011; 118(9):2454-65. PMC: 3298843. DOI: 10.1002/cncr.26492. View

16.

Heidegger I, Ofer P, Doppler W, Rotter V, Klocker H, Massoner P . Diverse functions of IGF/insulin signaling in malignant and noncancerous prostate cells: proliferation in cancer cells and differentiation in noncancerous cells. Endocrinology. 2012; 153(10):4633-43. DOI: 10.1210/en.2012-1348. View

17.

Jonasson J, Ljung R, Talback M, Haglund B, Gudbjornsdottir S, Steineck G . Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden. Diabetologia. 2009; 52(9):1745-54. DOI: 10.1007/s00125-009-1444-2. View

18.

Bjorge T, Lukanova A, Tretli S, Manjer J, Ulmer H, Stocks T . Metabolic risk factors and ovarian cancer in the Metabolic Syndrome and Cancer project. Int J Epidemiol. 2011; 40(6):1667-77. DOI: 10.1093/ije/dyr130. View

19.

Noto H, Goto A, Tsujimoto T, Noda M . Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One. 2012; 7(3):e33411. PMC: 3308971. DOI: 10.1371/journal.pone.0033411. View

20.

Wotton C, Yeates D, Goldacre M . Cancer in patients admitted to hospital with diabetes mellitus aged 30 years and over: record linkage studies. Diabetologia. 2010; 54(3):527-34. DOI: 10.1007/s00125-010-1987-2. View