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Bistable insulin response: The win-win solution for glycemic control.
Javed Akhtar1,2,3,4, Yukun Han3,4, Shangchen Han4
1School of Medicine|Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen 518172, China.
Iscience
|December 5, 2022
Summary
Muscles exhibit a bistable insulin response, crucial for safe and rapid blood sugar control. This switch-like mechanism, with specific thresholds, helps prevent both low and high blood sugar levels.
Area of Science:
- Biochemistry
- Physiology
- Mathematical Biology
Background:
- Glycemic control requires rapid and safe insulin response.
- Bistability in muscle insulin signaling is a theoretical prediction for achieving this control.
Purpose of the Study:
- To experimentally validate the bistability hypothesis of muscle insulin response.
- To investigate the in vitro and in vivo relevance of this bistability.
- To identify potential biomarkers for metabolic complications.
Main Methods:
- Cellular experiments using C2C12 myotubes.
- Single-cell analysis via Förster resonance energy transfer (FRET).
- Cultured cell analysis using immunoblotting.
- Mathematical modeling of glucose-insulin dynamics.
Main Results:
- Demonstrated bistable insulin response in C2C12 myotubes.
- Identified switch-on and switch-off thresholds at approximately 300 pM and 100 pM insulin, respectively.
- Mathematical model confirmed bistability's necessity for interpreting data and understanding glucose-insulin dynamics.
Conclusions:
- Bistability mediates the body's ability to prevent both hypoglycemia and hyperglycemia.
- The switch-on threshold serves as a potential biomarker for metabolic complications, linked to body composition.
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