Source comparison
MOTS-c for Metabolic Syndrome Research: Comparison of Key Study Protocols
Lee et al., Cell Metabolism (2021) Diet-induced obese mice (C57BL/6) 5mg/kg IP, 3×/week, 4 weeks 35% improvement in insulin sensitivity, 28% glucose tolerance increase AMPK activation, increased GLUT4 translocation, mitochondrial biogenesis Established MOTS-c
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- Lee et al., Cell Metabolism (2021)
- Diet-induced obese mice (C57BL/6)
- 5mg/kg IP, 3×/week, 4 weeks
- 35% improvement in insulin sensitivity, 28% glucose tolerance increase
- AMPK activation, increased GLUT4 translocation, mitochondrial biogenesis
- Established MOTS-c as a metabolic intervention distinct from insulin sensitisers. Effects persist in insulin-resistant states
- Reynolds et al., Diabetes (2023)
- Insulin receptor knockout mice
- 5mg/kg IP, 3×/week, 6 weeks
- Glucose lowering retained despite absent insulin signalling
- AMPK-dependent glucose uptake independent of insulin receptor phosphorylation
- Confirmed MOTS-c bypasses insulin pathways entirely, making it valuable for late-stage metabolic dysfunction models
- Kim et al., Molecular Metabolism (2022)
- High-fat diet mice
- 2.5mg/kg daily vs 5mg/kg 3×/week (same total weekly dose)
- Intermittent dosing produced 18% greater insulin sensitivity improvement
- Intermittent AMPK activation prevented receptor desensitisation
- Suggests dosing frequency impacts long-term efficacy more than total dose. Intermittent protocols may be superior for chronic studies
- Zhang et al., Nature Communications (2024)
- Human skeletal muscle cell culture
- 10μM, 24-hour incubation
- 42% increase in glucose uptake vs control, independent of insulin
- Direct ATIC binding confirmed via co-immunoprecipitation
- First human tissue validation of mechanism. Supports translational research applicability