Like other substrates, plasma glucose is in a dynamic state of constant turnover (i.e., rates of glucose appearance [Ra glucose] into and disappearance [Rd glucose] from the plasma) while staying within a narrow range of normal concentrations, a physiological priority. Persistent imbalance of glucose turnover leads to elevations (i.e., hyperglycemia, Ra>Rd) or falls (i.e., hypoglycemia, Ra<Rd) in the pool size, leading to clinical conditions such as diabetes. Endogenous Ra glucose is divided into hepatic glucose production via glycogenolysis and gluconeogenesis (GNG) and renal GNG. On the other hand, Rd glucose, the summed rate of glucose uptake by tissues/organs, involves various intracellular metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and oxidation at varying rates depending on the metabolic status. Despite the dynamic nature of glucose metabolism, metabolic studies typically rely on measurements of static, snapshot information such as the abundance of mRNAs and proteins and (in)activation of implicated signaling networks without determining actual flux rates. In this review, we will discuss the importance of obtaining kinetic information, basic principles of stable isotope tracer methodology, calculations of in vivo glucose kinetics, and assessments of metabolic flux in experimental models in vivo and in vitro.
Bibliographical noteFunding Information:
Il-Young Kim: Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07051053). Korea Research Fellowship (KRF) funded by the Ministry of Sciences and ICT and National Research Foundation of Korea (2019H1D3A-1A01071043). Sanghee Park: Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1I1A1A01074380). Cheol Soo Choi: This research was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No.2014M3A9D5A01073886). Sang-Hoon Suh: Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (No. 2017R1D1A1B03032988).
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism