glucagon-like-peptide-1 and Growth-Disorders

To test the hypothesis that neonatal GLP-1 exposure may program myosin heavy chain (MyHC) composition in adult skeletal muscle, two-day-old rats were transfected intramuscularly with vacant vector plasmid (VP), or recombinant plasmid expressing secretory GLP-1 at the doses of 60 microg (LG) and 120 microg (HG), respectively. Expression of GLP-1 mRNA was detected in muscles of both LG and HG rats 7 days after transfection, with more abundant GLP-1 transcript seen in LG rats. In accordance with the GLP-1 expression, LG rats demonstrated more significant responses to neonatal GLP-1 exposure. Small yet significant growth retardation was observed in LG rats, which is accompanied with significantly reduced serum insulin concentration at 8 weeks of age compared to VP rats. The responses of skeletal muscle were dependent on muscle type. Significant increase of PGC-1alpha and GLUT4 mRNA expression was detected in soleus of LG rats, whereas a MyHC type switch from IIB to I was seen in gastrocnemius. These results indicate that neonatal exposure of healthy pups to ectopic GLP-1 causes growth retardation with decreased serum insulin as well as muscle type-dependent modifications in MyHC type composition and metabolic gene expression in adult rats.

Topics: Age Factors; Animals; Animals, Newborn; Blood Glucose; Body Weight; Down-Regulation; Electroporation; Female; Glucagon-Like Peptide 1; Glucose Transporter Type 4; Growth Disorders; Injections, Intramuscular; Insulin; Male; Muscle, Skeletal; Myosin Heavy Chains; Organ Size; Pancreas; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Plasmids; Protein Isoforms; Rats; Rats, Wistar; RNA-Binding Proteins; RNA, Messenger; Transcription Factors; Transfection