Puerarin ameliorates skeletal muscle atrophy in STZ-induced type 1
diabetic rats by enhancing Akt/mTOR while inhibiting autophagy signaling
pathway
Abstract
Background and Purpose: Puerarin is an important isoflavone component
extracted from Pueraria lobate in traditional Chinese medicine. It has a
wide range of pharmacological effects. Increasing evidence indicates
that puerarin alleviates hyperglycemia and numerous related
complications. In this study, we explored the effect of puerarin on
skeletal muscle atrophy caused by type 1 diabetes in rats. Experimental
Approach: Male Sprague Dawley (SD) rats with streptozotocin
(STZ)-induced type 1 diabetes were used in this study. We measured
skeletal muscle weight, size and strength together with the
transformation of skeletal muscle types in type 1 diabetic rats.
Skeletal muscle L6 cells were used for in vitro study. Key Results:
Puerarin increased muscle tissue weights and improved muscle strength.
An enhanced skeletal muscle cross-sectional area was accompanied by
reduced mRNA expression of muscle atrophy marker genes, including F-box
only protein 32 (Atrogin-1) and muscle-specific RING-finger 1(Murf-1),
both in vitro and in vivo. The transformation from type I fibers (slow
muscle) to type II fibers (fast muscle) was also observed after puerarin
administration. In vitro studies suggested that puerarin upregulated
Akt/mTOR but downregulated the LC3/p62 signaling pathway, eventually
resulting in muscle hypertrophy. Conclusions and Implications: Our study
observed that puerarin mitigated skeletal muscle atrophy in type 1
diabetic rats. Subsequently, we found that the related mechanisms
closely involved the upregulation of protein synthesis via the Akt/mTOR
signaling pathway. Whether this anti-diabetic muscle atrophy effect in
mice applies to humans remains unknown.