Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
Clin Nutr. 2012 Dec;31(6):1002-7. doi: 10.1016/j.clnu.2012.05.011. Epub 2012 Jun 7.
Insulin resistance is perceived as deleterious, associated with conditions as the metabolic syndrome, type 2 diabetes mellitus and critical illness. However, insulin resistance is evolutionarily well preserved and its persistence suggests that it benefits survival. Insulin resistance is important in various states such as starvation, immune activation, growth and cancer, to spare glucose for different biosynthetic purposes such as the production of NADPH, nucleotides in the pentose phosphate pathway and oxaloacetate for anaplerosis. In these conditions, total glucose oxidation by the tricarboxylic acid cycle is actually low and energy demands are largely met by fatty acid and ketone body oxidation. This beneficial role of insulin resistance has consequences for treatment and research. Insulin resistance should be investigated at the cellular, tissue and whole organism level. The metabolic pathways discussed here, should be integrated in the accepted and valid mechanistic events of insulin resistance before interfering with them to promote insulin sensitivity at any cost.
胰岛素抵抗通常被认为是有害的，它与代谢综合征、2 型糖尿病和危重症等疾病有关。然而，胰岛素抵抗在进化上是很好的保存下来的，它的持续存在表明它有助于生存。胰岛素抵抗在各种状态下都很重要，如饥饿、免疫激活、生长和癌症，为不同的生物合成目的（如产生 NADPH、戊糖磷酸途径中的核苷酸和草酰乙酸用于补料）节省葡萄糖。在这些情况下，三羧酸循环的总葡萄糖氧化实际上很低，能量需求主要通过脂肪酸和酮体氧化来满足。胰岛素抵抗的这种有益作用对治疗和研究有影响。胰岛素抵抗应该在细胞、组织和整个生物体水平上进行研究。在以任何代价促进胰岛素敏感性之前，应该将这里讨论的代谢途径整合到公认的和有效的胰岛素抵抗机制事件中，以避免干扰它们。
