BETA-ENDORPHIN AND CORTICOTROPIN IMMUNOREACTIVITY AND SPECIFIC BINDING IN THE NEUROMUSCULAR SYSTEM OF OBESE-DIABETIC MICE

Immunoreactivity for two derivatives of pro-opiomelanocortin, beta-endorphin and alpha-melanocortin (or corticotropin), was demonstrated, using a conventional immunoperoxidase method, in some of the intramuscular nerves in muscle sections from obese diabetic (ob/ob) mice and homozygous lean (+/+) mice. The endplate regions were visualized in the sections by staining for acetylcholinesterase reaction product. The proportion of muscle endplates with beta-endorphin-immunoreactive motor nerves was approximately 2.5-fold higher in soleus and extensor digitorum longus muscles and approximately 1.5-fold higher in the diaphragm of the obese (ob/ob) mice compared to the normal lean mice. The proportion of muscle endplates with alpha-melanotropin-immunoreactive motor nerves was between 30 and 53% lower, depending on the muscle type, in the ob/ob mice compared to the lean mice. The muscles of ob/ob and lean mice were investigated for the presence of specific binding sites for [I-125]beta-endorphin and for [I-125]corticotropin, using autoradiography. Some muscle fibres in soleus, extensor digitorum longus and diaphragm in both the ob/ob and the lean mice exhibited specific binding sites for the radioactive ligands. The binding sites were distributed over the entire surface in these muscle fibres. In the ob/ob mice the number of muscle fibres with specific [I-125]beta-endorphin binding sites was six-fold higher in soleus and approximately 10-fold higher in extensor digitorum longus and diaphragm, than in the corresponding muscles of the lean mice. In contrast, the number of muscle fibres with specific [I-125]corticotropin binding sites was similar in obese (ob/ob) and lean mice. The results suggest a disturbance in the expression of pro-opiomelanocortin peptides in motoneurones of obese-diabetic (ob/ob) mice, and of the peptide receptors in the skeletal muscles. As there is a selective increase in beta-endorphin-immunoreactive nerves, the defect in peptide expression could be in the post-translational processing of the pro-opiomelanocortin precursor. The disturbance may be a manifestation of early neuropathic change.