糖尿病与肿瘤.ppt

糖尿病与癌症 主要内容 糖尿病、肥胖与肿瘤：流行病学的提示 糖尿病与肿瘤：潜在机制 糖尿病治疗与肿瘤 未来研究方向 肥胖：糖尿病与肿瘤的共同危险因子 主要内容 糖尿病、肥胖与肿瘤 糖尿病与肿瘤：可能潜在机制 糖尿病药物治疗与肿瘤 未来研究方向 在MCF7细胞系中甘精胰岛素促增殖作用明显高于其他胰岛素和胰岛素类似物 在MCF7细胞中治疗浓度的甘精胰岛素促增殖作用高于人胰岛素 研究目的及设计 探讨不同胰岛素类似物的使用及其使用剂量与长期肿瘤发生风险的关系 本研究克服了以往相关研究的不足1-4 - 巢式病例对照研究 - 多因素 logistic回归分析 - 纳入每种胰岛素平均日用剂量作为变量 研究流程 大剂量甘精胰岛素使用与肿瘤风险增加显著相关 甘精胰岛素呈剂量依赖性地与肿瘤风险增加相关 主要内容 糖尿病、肥胖与肿瘤 糖尿病与肿瘤：可能潜在机制 糖尿病药物治疗与肿瘤 未来研究方向 国内：宁光教授牵头研究 在NGT、IFG、IGT、DM人群中比较肿瘤的发病率 多中心、前瞻性队列研究 * Data from study with human insulin and a series of 6 analogues, measuring glucose transport in primary adipocytes and DNA synthesis in CHO cells. Mitogenic/metabolic potency ratio was independent of insulin receptor dissociation rate constant for values of Kd40%. NB that neither detemir or glargine were included in this analogue series; both have Kd 100% (Kurtzhals, 2000). These data show that it is important to keep off-rate above a critical thershold value below which mitogenic effects increase markedly. 资料来自对人胰岛素及6个胰岛素类似物的研究，检测原代脂肪细胞中葡萄糖转运及CHO细胞中DNA合成。当胰岛素受体解离速率常数（Kd）40%时，致有丝分裂/代谢能力的比值与Kd不再相关。说明：地特胰岛素和甘精胰岛素均未包括在这些类似物系列中，两者均Kd100% (Kurtzhals, 2000)。这些资料显示，保持解离速率高于一个关键阈值非常重要，低于这个阈值则致有丝分裂效应将明显增强。 ________________________________________ Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. 胰岛素类似物刺激胰岛素受体后的持续信号转导使致有丝分裂能力增强 Hansen BF, Danielsen GM, Drejer K, S?rensen AR, Wiberg FC, Klein HH, Lundemose AG. Health Care Discovery, Novo Nordisk A/S, Novo Alle, Bagsvaerd, Denmark. Biochem J. 1996 Apr 1;315 ( Pt 1):271-9. The metabolic and mitogenic potencies of six different insulin analogues were determined by measuring glucose transport in primary adipocytes and DNA synthesis in CHO cells respectively. Three analogues showed a disproportionately high mitogenic potency compared with their metabolic potency, and were up to 7 times more mitogenically than metabolically potent when compared with human insulin. The mitogenic/metabolic po