Insulin-Carcinogen or Mitogen? Preclinical and Clinical Evidence from Prostate, Breast, Pancreatic, and Colorectal Cancer Research
Insulin-Carcinogen or Mitogen? Preclinical and Clinical Evidence from Prostate, Breast, Pancreatic, and Colorectal Cancer Research
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DOI：
10.3810/pgm.2010.05.2153
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发表时间：
2010-05-01
影响因子：
4.2
通讯作者：
Riche, Daniel M.
中科院分区：
文献类型：
--
作者：
Call, Rosemary;Grimsley, Molly;Riche, Daniel M.
糖尿病是一种慢性疾病，影响2360万美国人，当身体不能产生内源性胰岛素或对内源性胰岛素产生抵抗力时就会发生。胰岛素作用的这种改变减少了葡萄糖转运蛋白4(GLUT4)受体的充分利用，GLUT4受体负责细胞葡萄糖摄取。因此，外源性给予人胰岛素及其类似物是降低1型和2型糖尿病发病率和死亡率的重要手段。根据2007年的估计，27%的糖尿病患者使用某种形式的胰岛素治疗。胰岛素利用率的增加已经成为一个令人担忧的问题，因为几项观察性试验的结果表明，这与罹患癌症的风险增加有关。为了帮助阐明使用胰岛素和癌症之间的潜在相互作用，我们搜索了PubMed和MEDLINE，以确定评估糖尿病治疗的致癌和/或有丝分裂潜力的文章，重点是胰岛素。我们综述的数据表明，胰岛素类似物，特别是甘精胰岛素，在不同类型的癌症中可能起到更多的促分裂作用而不是致癌作用，这表明在存在胰岛素类似物的情况下，现有肿瘤的生长速度被放大。胰岛素诱导有丝分裂的证据似乎在前列腺癌、乳腺癌、胰腺癌和结直肠癌中最为普遍。总而言之，目前胰岛素治疗在降低糖尿病发病率和死亡率方面的积极作用远远超过了风险。然而，临床医生必须勤奋地筛查接受胰岛素治疗的患者的新癌症，并监测现有癌症患者的肿瘤生长或维持缓解状态。
Diabetes mellitus is a chronic disease that affects > 23.6 million Americans, and occurs when the body is unable to produce or becomes resistant to endogenous insulin. This alteration of insulin's action reduces adequate utilization of glucose transporter type 4 (GLUT4) receptors, which are responsible for cellular glucose uptake. Thus, exogenous administration of human insulin and insulin analogs is an important modality used to reduce morbidity and mortality in both type 1 and type 2 diabetes. According to 2007 estimates, 27% of all patients with diabetes use some form of insulin therapy. The increasing utilization of insulin has become a cause for concern because findings from several observational trials have suggested an association with an increased risk of developing cancer. To help elucidate the potential interplay between insulin use and cancer, we searched PubMed and MEDLINE to identify articles that assessed the carcinogenic and/or mitogenic potential of diabetes treatments, focusing on insulin specifically. Data from our review suggest that insulin analogs, particularly insulin glargine, may play more of a mitogenic than a carcinogenic role in association with different types of cancer, suggesting an amplified rate of existing tumor growth in the presence of insulin analogs. Evidence for insulin-induced mitogenicity appears to be most prevalent in prostate, breast, pancreatic, and colorectal cancers. In conclusion, the positive effects of insulin therapy on reducing morbidity and mortality in diabetes greatly outweigh the risks at this time. However, clinicians must be diligent in both screening for new cancers in patients receiving insulin and in monitoring for tumor growth or maintenance of remission in patients with existing cancers.