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

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

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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Crossref · 10.1074/jbc.273.47.31160

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Citations

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Research works printed but not linked: 2

  1. Hill, 1984, Am. J. Physiol., 247, R318
  2. Himms-Hagen, 1994, Am. J. Physiol., 266, R1371

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Metadata

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
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
Licence
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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