Fisher W E, Boros L G, Schirmer W J
Department of Surgery, Ohio State University, Columbus 43210, USA.
Surgery. 1995 Aug;118(2):453-7; discussion 457-8. doi: 10.1016/s0039-6060(05)80358-7.
Epidemiologic and animal studies have linked pancreatic cancer growth with both diabetes and fat intake. This study examined the influence of insulin treatment on pancreatic cancer growth in diabetes. Diabetes-induced elevations in levels of glucose and free fatty acids were correlated with enhanced tumor growth both in vivo and in vitro.
Hamsters were divided into three groups: control (n = 15), streptozocin-diabetic (n = 20), or insulin-treated diabetic (n = 20). Diabetes was induced with streptozocin and treated with a continuous subcutaneous infusion of insulin delivered via osmotic pumps. Five x 10(5) H2T hamster pancreatic cancer cells were implanted into the cheek pouch. Levels of plasma glucose and fatty acids were measured, and their effect on H2T cell division was assessed in vitro with a spectrophotometric cell proliferation assay.
Levels of plasma glucose and fatty acids were elevated in streptozocin-diabetic animals and normalized with insulin treatment. After 21 days of growth, tumor weight was 36 mg in the control group, 156 mg in the diabetic group (p < 0.01 versus other groups), and 33 mg in the insulin-treated diabetic group. In vitro dose-dependent promotion of cell growth was shown for glucose (250%), linoleic acid (287%), linolenic acid (169%), and oleic acid (98%).
Insulin ameliorated enhanced tumor growth in this model of diabetes. Glucose and free fatty acids mobilized during diabetes may serve as fuel for established pancreatic cancers.
流行病学和动物研究已将胰腺癌的生长与糖尿病及脂肪摄入联系起来。本研究检测了胰岛素治疗对糖尿病状态下胰腺癌生长的影响。糖尿病引起的血糖和游离脂肪酸水平升高与体内外肿瘤生长增强相关。
仓鼠被分为三组：对照组（n = 15）、链脲佐菌素诱导糖尿病组（n = 20）或胰岛素治疗糖尿病组（n = 20）。用链脲佐菌素诱导糖尿病，并通过渗透泵持续皮下输注胰岛素进行治疗。将5×10⁵个H2T仓鼠胰腺癌细胞植入颊囊。测量血浆葡萄糖和脂肪酸水平，并通过分光光度法细胞增殖试验在体外评估它们对H2T细胞分裂的影响。
链脲佐菌素诱导糖尿病的动物血浆葡萄糖和脂肪酸水平升高，胰岛素治疗后恢复正常。生长21天后，对照组肿瘤重量为36 mg，糖尿病组为156 mg（与其他组相比，p < 0.01），胰岛素治疗糖尿病组为33 mg。体外实验显示，葡萄糖（250%）、亚油酸（287%）、亚麻酸（169%）和油酸（98%）呈剂量依赖性促进细胞生长。
在该糖尿病模型中，胰岛素改善了肿瘤生长增强的情况。糖尿病期间动员的葡萄糖和游离脂肪酸可能为已形成的胰腺癌提供燃料。
