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Intracerebroventricular neuropeptide Y infusion precludes inhibition of glucose and VLDL production by insulin.

Hoek, A.M. van den and Voshol, P.J. and Karnekamp, B.N. and Buijs, R.M. and Romijn, J.A. and Havekes, L.M. and Pijl, H. (2004) Intracerebroventricular neuropeptide Y infusion precludes inhibition of glucose and VLDL production by insulin. Diabetes, 53(10), 2529-2534. ISSN 00121797.

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Abstract

Recent evidence demonstrates that hypothalamic insulin signaling is required for inhibition of endogenous glucose production. The downstream mechanisms that are responsible for the effects of hypothalamic insulin receptor activation on hepatic fuel flux remain to be determined. To establish whether downregulation of neuropeptide Y (NPY) release by insulin is mandatory for its capacity to suppress glucose production, we examined the effects of a continuous intracerebroventricular (ICV) infusion of NPY (10 microg/h for 3-5 h) on glucose flux during a hyperinsulinemic-euglycemic clamp in mice. We also evaluated the effects of ICV NPY administration on free fatty acid and glycerol flux and VLDL production in this experimental context. In basal conditions, none of the metabolic parameters was affected by NPY infusion. In hyperinsulinemic conditions, peripheral glucose disposal was not different between vehicle- and NPY-infused animals. In contrast, hyperinsulinemia suppressed endogenous glucose production by approximately 8% vs. 30% in NPY- vs. vehicle-infused mice, respectively (P \< 0.05). Also, VLDL production was significantly higher during hyperinsulinemia in NPY- compared with vehicle-infused mice (97.5 +/- 18.0 vs. 54.7 +/- 14.9 micromol. kg(-1). h(-1); P \< 0.01). These data suggest that the neurophysiological action of insulin to downregulate hypothalamic NPY release is a prerequisite for its ability to suppress hepatic fuel production, whereas it is not mandatory for its capacity to modulate glucose disposal or lipolysis.

Item Type:Article
Institutes:Netherlands Institute for Neuroscience (NIN)
ID Code:3654
Deposited On:13 Feb 2009 17:14
Last Modified:10 Dec 2009 13:14

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