Loss of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Regulation and Limits Exercise Capacity
Ji-Hyun Lee1, Ik-Rak Jung1, Becky Tu-Sekine1
1Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, MD 21218, USA.
International Journal of Molecular Sciences
|March 27, 2025
Summary
Skeletal muscle inositol polyphosphate multikinase (IPMK) deletion increases body weight and impairs glucose tolerance. Loss of IPMK in muscle disrupts lipid metabolism and reduces exercise capacity, suggesting IPMK as a target for metabolic syndrome treatments.
Area of Science:
- Biochemistry
- Metabolic pathways
- Cellular signaling
Background:
- Inositol phosphates are key signaling molecules.
- Inositol polyphosphate multikinase (IPMK) regulates inositol phosphate metabolism.
- IPMK's systemic metabolic role is largely unknown.
Purpose of the Study:
- To investigate the systemic metabolic impact of skeletal muscle IPMK deletion.
- To understand IPMK's role in energy homeostasis and muscle function.
Main Methods:
- Development of a skeletal muscle-specific IPMK knockout mouse model (IPMK-MKO).
- Assessment of body weight, glucose tolerance (GTT), and exercise capacity.
- Analysis of skeletal muscle triglyceride content and fatty acid oxidation (β-oxidation).
Main Results:
- IPMK-MKO mice showed a 12% increase in body weight and impaired glucose tolerance.
- Exercise capacity was reduced by 45% in IPMK-MKO mice.
- Skeletal muscle triglyceride accumulation increased 2.5-fold, with a 30% decrease in β-oxidation rates.
Conclusions:
- Skeletal muscle IPMK is crucial for maintaining whole-body energy homeostasis.
- IPMK deficiency in muscle leads to metabolic dysfunction, including obesity and impaired lipid metabolism.
- Targeting IPMK could offer a therapeutic strategy for metabolic syndromes.
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