CoChat
Sign Up
Cited by 223Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesPancreatic function and diabetes

Intracerebroventricular Leptin Regulates Hepatic but Not Peripheral Glucose Fluxes

Open access
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
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1074/jbc.273.47.31160

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The effect of leptin on glucose metabolism is similar whether leptin is administered intravenously or via intracerebroventricular infusion at much lower doses in both rats and mice.

    “the effect is similar whether leptin is administered i.v. or via i.c.v. infusion (at much lower doses) in both rats (106) and mice (91).”

    From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [106]

  • In normal rats, i.c.v. leptin administration stimulates hepatic gluconeogenesis but does not affect overall hepatic glucose production owing to a simultaneous decrease of glycogenolysis.

    “In normal rats, i.c.v. leptin administration stimulates hepatic gluconeogenesis, but fails to affect overall hepatic glucose production owing to a simultaneous decrease of glycogenolysis (106).”

    From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [106]

  • The antidiabetic effect of CNS leptin is distinct from leptin's previously reported effect to increase hepatic insulin sensitivity.

    “This leptin action is distinct from its previously reported effect to increase insulin sensitivity in the liver and offers compelling evidence that the brain has the capacity to normalize diabetic hyperglycemia in the presence of sufficient amounts of central nervous system leptin.”

    From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [10]

  • Accumulating evidence suggests that leptin, insulin, and nutrient-related signals in the CNS improve hepatic insulin sensitivity.

    “Although accumulating evidence suggests that leptin (10 -13), insulin (14,15), and nutrient-related signals (16 -18) in the CNS improve hepatic insulin sensitivity”

    From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [10]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Surgery › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review