Effects of streptozotocin-induced diabetes mellitus and insulin treatment on neuropeptide Y mRNA in the rat hypothalamus.

Levels of neuropeptide Y and neuropeptide Y mRNA are increased in the arcuate nucleus of severely diabetic rats which may be the result of the associated marked hypoinsulinaemia. We hypothesised that if neuropeptide Y mRNA is regulated by physiological changes in circulating insulin, then the relatively minor changes in circulating insulin found in mild diabetes would also affect neuropeptide Y expression and its response to changing insulin levels should be rapid. Neuropeptide Y mRNA was quantified by in situ hybridisation through the rostral, mid and caudal levels of the arcuate nucleus of adult female rats. Neuropeptide Y mRNA was significantly increased at all three levels of the arcuate nucleus, 7 days after i.v. administration of 40 mg/kg streptozotocin. Neuropeptide Y mRNA was not further increased in the arcuate nucleus of animals given 50 mg/kg streptozotocin. In the former group, serum glucose was increased but insulin levels and body weights were the same as in control rats. In the 50 mg/kg streptozotocin group, serum glucose was further increased while serum insulin and body weight were reduced. In addition, neuropeptide Y mRNA was not altered in the hypothalamic dorsomedial nucleus or the thalamic reticular nucleus. When diabetic rats were treated for 20 h with s.c. insulin, there was decreased neuropeptide Y mRNA in the arcuate nucleus. We conclude that neuropeptide Y mRNA in the arcuate nucleus is responsive to small changes in circulating insulin levels and the response occurs within 20 h. These data support that circulating insulin may contribute to control of neuropeptide Y expression under physiological conditions.