INTRACEREBROVENTRICULAR ADMINISTRATION OF NEUROPEPTIDE-Y TO NORMAL RATS HAS DIVERGENT EFFECTS ON GLUCOSE-UTILIZATION BY ADIPOSE-TISSUE AND SKELETAL-MUSCLE

Given that several genetically obese rodents characterized by hyperpha gia, hyperinsulinemia, and insulin resistance have increased hypothala mic neuropeptide Y (NPY) mRNA and peptide content, the impact of NPY a dministered intracerebroventricularly (i.c.v.) for 7 days to normal, a wake rats was investigated. NPY produced marked hyperphagia, increased body weight gain, increased basal insulinemia, and, more importantly, a much greater insulin response to meal feeding than that of saline-i nfused controls. NPY administration also resulted in a pronounced incr ease in the in vivo insulin-stimulated glucose uptake by adipose tissu e but in a marked decrease in uptake by eight different muscle types. Increased insulin responsiveness of the glucose transport process by a dipose tissue was accompanied by increases in both GLUT4 mRNA and prot ein levels. In contrast, the decreased insulin responsiveness of gluco se uptake in muscles from NPY-administered rats was not related to GLU T4 expression. We conclude that i.c.v. NPY administration to normal ra ts produces a hormonal-metabolic situation that is similar to that rep orted in the dynamic phase of the genetic obesity of the fa/fa strain. Thus, NPY could be of primary importance in the establishment of obes ity syndromes with incipient insulin resistance.