Qingwen Jia, Xiaohan Chen, Yuping Jia, Xixi Dou, Lewis Ezeogu, Ningzhi Xu and D Joshua Liao
All biological functions should have a structural basis. Any functional change should be due to an alteration in the related structure. If a functional change is irreversible, it should be due to the irreversibility of the structural alteration. For instance, cancer is irreversible because cancer cells have irreversible genetic mutations. However, Type 2 Diabetes (T2D) with Insulin-Resistance (IR) as a central mechanism is irreversible but seems to lack a corresponding irreversible structural change. IR and T2D exhibit many abnormalities that are attributable to altered mitochondria or altered cellular RNAs, proteins, lipids, etc. without genetic mutations involved. These alterations are reversible, because mitochondrial biogenesis can be induced by such as exercise whereas RNAs, proteins and lipids will degrade after some time. Aging is irreversible but many aging manifestations also lack corresponding permanent structural changes, and IR may be one such manifestation. IR affects mainly striated muscles, adipose tissue, brain and liver that are collectively defined herein as the “catabolic cell type” for their low proliferation rates but high metabolism of glucose via oxidation-phosphorylation in mitochondria. In contrast, fast-proliferating cells are defined as the “anabolic cell type” because they are the main cancer origins and often metabolize glucose via glycolysis. Dichotomizing T2D- and cancer-targeted cells and pointing out that the irreversible IR as an aging phenomenon lacks a corresponding irreversible structural change may help understand the differences between, and the mechanisms of, T2D and cancer, although these concepts challenge the “structural-functional relationship” dogma in not only biology but also philosophy.