Neonatal intramuscular injection of plasmid DNA encoding GLP-1 reduces serum insulin level and modifies skeletal muscle myosin heavy chain composition in adult rats.
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.
Wang
L
L
Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, China.
Guo
F
F
Wei
S
S
Zhao
R
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D015536:Down-Regulation; D018274:Electroporation; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis* / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism; D007273:Injections, Intramuscular; D007328:Insulin / Q000097:blood*; D008297:Male; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D010179:Pancreas / Q000254:growth & development / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010957:Plasmids / Q000008:administration & dosage*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; D052216:Glucagon-Like Peptide 1; D018995:Myosin Heavy Chains