The Journal of Clinical Endocrinology and Metabolism Journal Article

Hyperglycemia and Muscle Lipids

August 09, 2022
 

Christopher E Shannon, Aurora Merovci, Marcel Fourcaudot, Devjit Tripathy, Muhammad Abdul-Ghani, Hu Wang, Xianlin Han, Luke Norton, Ralph A DeFronzo
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 8, August 2022, Pages e3177–e3185
https://doi.org/10.1210/clinem/dgac306

Abstract

Context

Sustained increases in plasma glucose promote skeletal muscle insulin resistance independent from obesity and dyslipidemia (ie, glucotoxicity). Skeletal muscle lipids are key molecular determinants of insulin action, yet their involvement in the development of glucotoxicity is unclear.

Objective

To explore the impact of mild physiologic hyperglycemia on skeletal muscle lipids.

Design

Single group pretest-posttest.

Participants

Healthy males and females with normal glucose tolerance.

Interventions

72-hour glucose infusion raising plasma glucose by ∼50 mg/dL.

Main Outcome Measures

Skeletal muscle lipids, insulin sensitivity, lipid oxidation.

Results

Despite impairing insulin-mediated glucose disposal and suppressing fasting lipid oxidation, hyperglycemia did not alter either the content or composition of skeletal muscle triglycerides, diacylglycerides, or phospholipids. Skeletal muscle ceramides decreased after glucose infusion, likely in response to a reduction in free fatty acid concentrations.

Conclusions

Our results demonstrate that the major lipid pools in skeletal muscle are unperturbed by sustained increases in glucose availability and suggest that glucotoxicity and lipotoxicity drive insulin resistance through distinct mechanistic pathways.

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