Effects of luseogliflozin treatment on hyperglycemia-induced muscle atrophy in rats

Area of Science:

• Endocrinology
• Metabolism
• Muscle Physiology

Background:

• Diabetes mellitus is a known risk factor for sarcopenia.
• Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors like luseogliflozin improve hyperglycemia, reducing inflammation and oxidative stress.
• The impact of SGLT2 inhibitors on skeletal muscle mass and function in hyperglycemia remains unclear.

Purpose of the Study:

• To investigate the effects of luseogliflozin on preventing muscle atrophy in a rodent model of hyperglycemia.
• To determine if luseogliflozin-mediated attenuation of hyperglycemia impacts skeletal muscle regulation.

Main Methods:

• A hyperglycemic rodent model was established using streptozotocin.
• Rats were divided into four groups: control, control with SGLT2 inhibitor, hyperglycemia, and hyperglycemia with SGLT2 inhibitor.
• Muscle atrophy was assessed in relation to hyperglycemia suppression by luseogliflozin.

Main Results:

• Luseogliflozin treatment inhibited muscle atrophy in streptozotocin-induced hyperglycemic rats.
• The drug suppressed hyperglycemia-mediated increases in advanced glycation end products (AGEs).
• Luseogliflozin treatment inhibited the activation of the protein degradation pathway in muscle cells.

Conclusions:

• Luseogliflozin can prevent muscle atrophy associated with hyperglycemia.
• The protective effect is partly mediated by inhibiting AGEs and mitigating mitochondrial dysfunction-induced muscle degradation.
• SGLT2 inhibition shows potential for preserving skeletal muscle mass in diabetic conditions.