Kapelner Adam, Vorsanger Matthew
Department of Mathematics, Queens College, City University of New York, 65-30 Kissena Blvd., Queens, NY 11367, United States.
Department of Cardiology, New York University, 550 First Avenue, New York, NY 10016, United States.
Med Hypotheses. 2015 Mar;84(3):162-8. doi: 10.1016/j.mehy.2014.11.002. Epub 2014 Dec 10.
Neoplasms are highly dependent on glucose as their substrate for energy production and are generally not able to catabolize other fuel sources such as ketones and fatty acids. Thus, removing access to glucose has the potential to starve cancer cells and induce apoptosis. Unfortunately, other body tissues are also dependent on glucose for energy under normal conditions. However, in human starvation (or in the setting of diet-induced ketogenesis), the body "keto-adapts" and glucose requirements of most tissues drop to almost nil. Exceptions include the central nervous system (CNS) and various other tissues which have a small but obligatory requirement of glucose. Our hypothesized treatment takes keto-adaptation as a prerequisite. We then propose the induction of severe hypoglycemia by depressing gluconeogenesis while administering glucose to the brain. Although severe hypoglycemia normally produces adverse effects such as seizure and coma, it is relatively safe following keto-adaptation. We hypothesize that our therapeutic hypoglycemia treatment has potential to rapidly induce tumor cell necrosis.
肿瘤高度依赖葡萄糖作为其能量产生的底物,通常无法分解代谢其他燃料来源,如酮体和脂肪酸。因此,切断葡萄糖供应有可能使癌细胞饥饿并诱导其凋亡。不幸的是,在正常情况下,身体的其他组织也依赖葡萄糖提供能量。然而,在人类饥饿状态(或饮食诱导生酮的情况下),身体会发生“酮适应”,大多数组织对葡萄糖的需求几乎降至零。例外情况包括中枢神经系统(CNS)和其他各种对葡萄糖有少量但必需需求的组织。我们假设的治疗方法以酮适应为前提。然后,我们建议在向大脑输送葡萄糖的同时,通过抑制糖异生来诱导严重低血糖。虽然严重低血糖通常会产生癫痫和昏迷等不良反应,但在酮适应后相对安全。我们推测,我们的治疗性低血糖疗法有可能迅速诱导肿瘤细胞坏死。