Inhibition of hypothalamic neuropeptide Y gene expression by insulin.

作者：Michael W. Schwartz, Alfred J. Sipols, Jonathan Lewis Marks, Gerard Sanacora, Jeffrey D. White, A.J.W. Scheurink, Steven E. Kahn, D G Baskin, Stephen C. Woods, D.P. Figlewicz · 发表于：Endocrinology · 年份：1992 · DOI：10.1210/endo.130.6.1597158 · 被引用次数：537 · 研究领域：Neuropeptides and Animal Physiology、Regulation of Appetite and Obesity、Pancreatic function and diabetes

Insulin acts in the brain to suppress feeding, whereas neuropeptide Y (NPY) has the opposite effect. Since fasting lowers plasma insulin levels and increases hypothalamic synthesis of NPY, we proposed that insulin may inhibit hypothalamic NPY gene expression. To test this hypothesis, we used RIA and in situ hybridization histochemistry to determine if centrally administered insulin could reduce levels of both NPY and its messenger RNA (mRNA) in discreet hypothalamic regions during fasting. Three groups of Long-Evans rats were entered into a 72-h study protocol. One group was fed ad libitum during this period, while the others were fasted. Fed rats received intracerebroventricular (icv) injections of saline vehicle at 12-h intervals, whereas fasted groups received icv vehicle alone or with insulin (4 mU/12 h). In vehicle-only treated rats, fasting significantly increased expression of preproNPY mRNA in the arcuate nucleus to 179 +/- 20% of fed controls. Administration of icv insulin during fasting abolished this increase (99 +/- 14% of fed controls; P less than 0.05 vs. fasted, vehicle-treated rats). Central insulin administration during fasting also reduced immunoreactive NPY concentrations in samples punched from the paraventricular nucleus (PVN) (875 +/- 122 pg/punch) to levels below vehicle-only treated rats (1396 +/- 435 pg/punch; P less than 0.05), similar to free-feeding control values (814 +/- 170 pg/punch). By comparison, neither fasting nor central insulin administra...