Knockdown of neuropeptide y in the dorsomedial hypothalamus promotes hepatic insulin sensitivity in male rats

Lin Li, C. Barbier De La Serre, Ni Zhang, Liang Yang, Hong Li, Sheng Bi

Research output: Contribution to journalArticle


Recent evidence has shown that alterations in dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) signaling influence glucose homeostasis, but the mechanism through which DMH NPY acts to affect glucose homeostasis remains unclear. Here we report that DMH NPY descending signals to the dorsal motor nucleus of the vagus (DMV) modulate hepatic insulin sensitivity to control hepatic glucose production in rats. Using the hyperinsulinemic-euglycemic clamp,werevealed that knockdown of NPY in the DMH by adeno-associated virus-mediated NPY-specific RNAi promoted insulin's action on suppression of hepatic glucose production. This knockdown silenced DMH NPY descending signals to the DMV, leading to an elevation of hepatic vagal innervation. Hepatic vagotomy abolished the inhibitory effect ofDMHNPY knockdown on hepatic glucose production, but this glycemic effect was not affected by vagal deafferentation. Together, these results demonstrate a distinct role forDMHNPY in the regulation of glucose homeostasis through the hepatic vagal efferents and insulin action on hepatic glucose production.

Original languageEnglish (US)
Pages (from-to)4842-4852
Number of pages11
Issue number12
Publication statusPublished - Dec 1 2016


ASJC Scopus subject areas

  • Endocrinology

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