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Beta2-agonist Impairs Muscle Insulin Sensitivity in Persons With Insulin Resistance.

Beta2-agonist Impairs Muscle Insulin Sensitivity in Persons With Insulin Resistance.

Authors :
Onslev, Johan
Fiorenza, Matteo
Thomassen, Martin
Havelund, Jesper
Bangsbo, Jens
Færgeman, Nils
Wojtaszewski, Jørgen F P
Hostrup, Morten
Source :
Journal of Clinical Endocrinology & Metabolism; Jan2025, Vol. 110 Issue 1, p275-288, 14p
Publication Year :
2025

Abstract

Context Given the promising effects of prolonged treatment with beta<subscript>2</subscript>-agonist on insulin sensitivity in animals and nondiabetic individuals, the beta<subscript>2</subscript>-adrenergic receptor has been proposed as a target to counter peripheral insulin resistance. On the other hand, rodent studies also reveal that beta<subscript>2</subscript>-agonists acutely impair insulin action, posing a potential caveat for their use in treating insulin resistance. Objective To assess the impact of beta<subscript>2</subscript>-agonist on muscle insulin action and glucose metabolism and identify the underlying mechanism(s) in 10 insulin-resistant subjects. Methods and participants In a crossover design, we assessed the effect of beta<subscript>2</subscript>-agonist on insulin-stimulated muscle glucose uptake during a 3-hour hyperinsulinemic isoglycemic clamp with and without intralipid infusion in 10 insulin-resistant, overweight subjects. Two hours into the clamp, we infused beta<subscript>2</subscript>-agonist. We collected muscle biopsies before, 2 hours into, and by the end of the clamp and analyzed them using metabolomic and lipidomic techniques. Results We establish that beta<subscript>2</subscript>-agonist, independently from and additively to intralipid, impairs insulin-stimulated muscle glucose uptake via different mechanisms. In combination, beta<subscript>2</subscript>-agonist and intralipid nearly eliminates insulin-dependent muscle glucose uptake. Although both beta<subscript>2</subscript>-agonist and intralipid elevated muscle glucose-6-phosphate, only intralipid caused accumulation of downstream muscle glycolytic intermediates, whereas beta<subscript>2</subscript>-agonist attenuated incorporation of glucose into glycogen. Conclusion Our findings suggest that beta<subscript>2</subscript>-agonist inhibits glycogenesis, whereas intralipid inhibits glycolysis in skeletal muscle of insulin-resistant individuals. These results should be addressed in future treatment of insulin resistance with beta<subscript>2</subscript>-agonist. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0021972X
Volume :
110
Issue :
1
Database :
Complementary Index
Journal :
Journal of Clinical Endocrinology & Metabolism
Publication Type :
Academic Journal
Accession number :
181987328
Full Text :
https://doi.org/10.1210/clinem/dgae381