Affordable Access

deepdyve-link
Publisher Website

Long acting GLP-1 analog liraglutide ameliorates skeletal muscle atrophy in rodents.

Authors
  • Gurjar, Anagha Ashok1
  • Kushwaha, Sapana2
  • Chattopadhyay, Sourav1
  • Das, Nabanita2
  • Pal, Subhashis3
  • China, Shyamsundar Pal4
  • Kumar, Harish2
  • Trivedi, Arun Kumar1
  • Guha, Rajdeep5
  • Chattopadhyay, Naibedya4
  • Sanyal, Sabyasachi6
  • 1 Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow 226031, India. , (India)
  • 2 Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India. , (India)
  • 3 Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, India. , (India)
  • 4 Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226031, India; AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow 226031, India. , (India)
  • 5 AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow 226031, India; Laboratory Animals Facility CSIR-Central Drug Research Institute, Lucknow 226031, India. , (India)
  • 6 Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India; AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow 226031, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
Metabolism: clinical and experimental
Publication Date
Dec 05, 2019
Pages
154044–154044
Identifiers
DOI: 10.1016/j.metabol.2019.154044
PMID: 31812628
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Skeletal muscle atrophy is characterized by muscle wasting with partial or complete functional loss. Skeletal muscle atrophy severely affects the quality of life and currently, there is no available therapy except for spinal muscular atrophy. Drug repositioning is a promising strategy that reduces cost and time due to prior availability of safety and toxicity details. Here we investigated myogenic and anti-atrophy effects of glucagon-like peptide-1 (GLP-1) analog liraglutide. We used several in vitro atrophy models in C2C12 cells and in vivo models in Sprague Dawley rats to study Liraglutide's efficacy. QPCR and western blotting were used to assess cAMP-dependent signaling pathways specifically activated by liraglutide. Therapeutic efficacy of liraglutide was investigated by histological analysis of transverse muscle sections followed by morphometry. Myogenic capacity was investigated by immunostaining for myogenic factors. Liraglutide induced myogenesis in C2C12 myoblasts through GLP-1 receptor via a cAMP-dependent complex network of signaling events involving protein kinase A, phosphoinositide 3-kinase/protein kinase B, p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. Liraglutide imparted protection against freeze injury, denervation, and dexamethasone -induced skeletal muscle atrophy and improved muscular function in all these models. In a therapeutic mode, liraglutide restored myofibrillar architecture in ovariectomy-induced atrophy. Anti-atrophy actions of liraglutide involved suppression of atrogene expression and enhancement in expression of myogenic factors. Liraglutide imparted protection and restored myofybrillar architecture in diverse models of muscle atrophy. Given its potent anti-atrophy, and recently reported osteoanabolic effects, we propose liraglutide's clinical evaluation in skeletal muscle atrophy and musculoskeletal disorders associated with diverse pathologies. Copyright © 2019. Published by Elsevier Inc.

Report this publication

Statistics

Seen <100 times