Intracerebroventricular Neuropeptide Y Infusion Precludes Inhibition of Glucose and VLDL Production by Insulin
Open accessAbstract
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 μg/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 ∼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 μmol · 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.
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Central administration of NPY and the melanocortin-3/4 receptor antagonist SHU9119 causes insulin resistance and glucose intolerance via mechanisms independent of food intake.
“Central administration of both NPY and the melanocortin-3/4 receptor antagonist, SHU9119, cause insulin resistance and glucose intolerance via mechanisms independent of their effects on food intake (1, 109, 188).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [188]
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Self-citation
- Authors
- van den Hoek, A. M., Voshol, P. J., Karnekamp, B. N., Buijs, R. M., Romijn, J. A., Havekes, L. M., & Pijl, H.
- Affiliations
- Organization of Applied Scientific Research-Prevention and Health, Gaubius Laboratory, Leiden, the Netherlands
- Leiden University Medical Center (NL)
- Netherlands Institute for Brain Research, Amsterdam, the Netherlands
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-10-01
- Volume
- 53
- Issue
- 10
- Pages
- 2529-2534
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2112743857
- Cited by
- 109
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2021: 2 · 2019: 3 · 2018: 1 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 9 · 2013: 14 · 2012: 6
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- TNO Repository (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- neuropeptide Y, hepatic glucose production, VLDL production, hyperinsulinemic-euglycemic clamp, intracerebroventricular infusion, insulin receptor, lipolysis, glucose disposal
- MeSH terms
- Animals, Blood Glucose, Cerebral Ventricles, Fatty Acids, Nonesterified, Glucose, Glycerol, Hyperinsulinism, Infusions, Parenteral, Insulin, Kinetics, Lipoproteins, VLDL, Neuropeptide Y, Glucose Clamp Technique, Mice
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