Bistable insulin response: The win-win solution for glycemic control

• Published in: iScience 2022-12, Vol.25 (12), p.105561-105561, Article 105561
• Main Authors: Akhtar, Javed, Han, Yukun, Han, Shangchen, Lin, Weiping, Cao, Chenyu, Ge, Ruowen, Babarinde, Isaac Adeyemi, Jia, Qingzhao, Yuan, Yueyang, Chen, Guangming, Zhao, Yajie, Ye, Richard, Liu, Guozhen, Chen, Luonan, Wang, Guanyu
• Format: Article
• Language: English
• Subjects: Human metabolism; mathematical biosciences
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105561

To satisfy both the safety and rapidity of glycemic control, muscles’ insulin response must be bistable, as theoretically predicted. Here, we test the bistability hypothesis by combining cellular experiments (to measure the threshold values in vitro) with mathematical modeling (to test the relevance of bistability in vivo). We examine bistability in C2C12 myotubes by both single-cell analysis (Fӧrster resonance energy transfer) and cultured cells analysis (immunoblot). These technologies demonstrate bistable insulin response, with typical switch-on and switch-off thresholds of approximately 300 and 100 pM, respectively. Our mathematical model demonstrates the indispensability of bistability in interpreting experimental data, reveals fine details of plasma glucose-insulin dynamics, and explains unclear phenomena. These results suggest that the body’s ability to simultaneously avoid both hypoglycemia and hyperglycemia is mediated by bistability. The switch-on threshold is a promising biomarker for metabolic complications due to its deep quantitative connection with body composition, which is easy to measure. [Display omitted] •C2C12 derived myotube exhibits bistable response to insulin•Bistable insulin response is the win-win solution for glycemic control•Peripheral insulin resistance is a good indicator of body fatness•Reactive hypoglycemia may root in insulin response hysteresis Human metabolism; Mathematical biosciences