Cited by 222Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesPancreatic function and diabetes

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Intracerebroventricular Leptin Regulates Hepatic but Not Peripheral Glucose Fluxes

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Liu, LiSen, Karkanias, George B., Morales, Jose' C., Hawkins, Meredith, Barzilai, Nir, Wang, Jiali, Rossetti, Luciano·1998·Journal of Biological Chemistry

DOI 10.1074/jbc.273.47.31160

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Abstract

Acute intravenous infusions of leptin markedly alter hepatic glucose fluxes (Rossetti, L., Massillon, D., Barzilai, N., Vuguin, P., Chen, W., Hawkins, M., Wu, J., and Wang, J. (1997) J. Biol. Chem. 272, 27758-22763). Here we examine whether intracerebroventricular (ICV) leptin administration regulates peripheral and hepatic insulin action. Recombinant mouse leptin (n = 14; 0.02 or 1 microgram/kg.h) or vehicle (n = 9) were administered ICV for 6 h to conscious rats, and insulin action was determined by insulin (3 milliunits/kg.min) clamp and tracer dilution techniques. During physiologic hyperinsulinemia (approximately 65 microunits/ml), the rates of glucose uptake (Rd, 20.1 +/- 0.6 and 23.1 +/- 0.7 versus 21.7 +/- 0.6 mg/kg.min; p = NS), glycolysis and glycogen synthesis were similar in rats receiving low- and high-dose leptin versus vehicle. ICV leptin resulted in a 2-3-fold increase in hepatic phosphoenolpyruvate carboxykinase mRNA levels. Glycogenolysis and PEP-gluconeogenesis (2.1 +/- 0.3 mg/kg. min) contributed similarly to endogenous glucose production (GP) in the vehicle-infused group. However, gluconeogenesis accounted for approximately 80% of GP in both groups receiving ICV leptin, while hepatic glycogenolysis was markedly suppressed (0.7 +/- 0.3 and 1.2 +/- 0.3 versus 2.2 +/- 0.4 mg/kg.min, in rats receiving low- and high-dose leptin versus vehicle, respectively; p < 0.01). In summary, short-term ICV leptin administration: 1) failed to affect peripheral insulin action, but 2) induced a striking re-distribution of intrahepatic glucose fluxes. The latter effect largely reproduced that of leptin given systemically at much higher doses. Thus, the regulation of hepatic glucose fluxes by leptin is largely mediated via its central receptors.

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Self-citation
Leptin: A Metabolic Perspective
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Authors: Liu, L., Karkanias, G. B., Morales, J. C., Hawkins, M., Barzilai, N., Wang, J., & Rossetti, L.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Rossetti, Luciano
ORCID: Karkanias, George B.
Hawkins, Meredith
Barzilai, Nir
Wang, Jiali
Rossetti, Luciano
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1998-11
Volume: 273
Issue: 47
Pages: 31160-31167
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.273.47.31160
OpenAlex: W2001716823
Cited by: 222
References: 41
Citations by year: 2024: 2 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 1 · 2018: 3 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 3 · 2013: 5 · 2012: 7
FWCI: 3.75
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 8004 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-45024, R01DK045024, R01-DK 48321, R01DK048321, DK20541)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: leptin, intracerebroventricular administration, insulin action, gluconeogenesis, glycogenolysis, endogenous glucose production, phosphoenolpyruvate carboxykinase, hepatic glucose uptake, hyperinsulinemia
MeSH terms: Animals, Blood Glucose, Carboxy-Lyases, Cerebral Ventricles, Drug Administration Routes, Glucose, Glycogen, Glycolysis, Infusions, Intra-Arterial, Infusions, Parenteral, Insulin, Liver, Male, Proteins, Glucose Clamp Technique, Rats, Sprague-Dawley, Leptin, Mice, Rats

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Intracerebroventricular Leptin Regulates Hepatic but Not Peripheral Glucose Fluxes

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