The role of glucagon-like peptides in osteosarcopenia.

Abstract

Various metabolic abnormalities including obesity, insulin resistance, hypertension, dyslipidemia, hyperthyroidism, and low vitamin D levels have been linked to both osteopenia and sarcopenia. Osteo-sarcopenia is also commonly observed due to aging that notably include postmenopausal women. GLP-1, a labile incretin secreted from the intestinal L-cells stimulates insulin secretion and sensitivity, making it an effective anti-diabetic medication. GLP-1 binds to its receptor, the GLP-1 receptor, a G-protein-coupled receptor, and leads to the stimulation of adenylate cyclase, increasing the levels of cyclic AMP (cAMP). Elevated cAMP then activates protein kinase A and other downstream signaling pathways. These signaling cascades result in various cellular responses, such as enhanced insulin secretion from pancreatic beta cells, improved insulin sensitivity, and modulation of appetite and gastric emptying. Additionally, GLP-1 signaling can promote cell growth and survival, contributing to its effects on muscle and bone health. Its role as an anti-diabetic medication has been enhanced through various modifications to extend its half-life, thereby improving its effectiveness and druggability. GLP-1 analogs, initially developed for diabetes management, have also been harnessed for obesity treatment due to the effect of GLP-1 to induce satiety and slow gastric emptying. Beyond their well-known anti-diabetic and anti-obesity effects, GLP-1 agonists can enhance muscle mass and bone density, making them valuable in addressing conditions like sarcopenia and osteoporosis. This review focuses on the effects of GLP-1 analogs on musculoskeletal health, by critically assessing the underlying signaling mechanisms in order to understand their translational potential for the treatment of osteo-sarcopenia.