Cited by 304Regulation of Appetite and ObesityPancreatic function and diabetesAdipokines, Inflammation, and Metabolic Diseases

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Short Term Effects of Leptin on Hepatic Gluconeogenesis and in Vivo Insulin Action

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Rossetti, Luciano, Massillon, Duna, Barzilai, Nir, Vuguin, Patricia, Chen, Wei, Hawkins, Meredith, Wu, Jie, Wang, Jali·1997·Journal of Biological Chemistry

DOI 10.1074/jbc.272.44.27758

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Abstract

Long term administration of leptin decreases caloric intake and fat mass and improves glucose tolerance. Here we examine whether leptin acutely regulates peripheral and hepatic insulin action. Recombinant mouse leptin (0.3 mg/kg.h, Leptin +) or vehicle (Leptin -) were administered for 6 h to 4-month-old rats (n = 20), and insulin (3 milliunits/kg.min) clamp studies were performed. During physiologic hyperinsulinemia (plasma insulin approximately 65 microunits/ml), the rates of whole body glucose uptake, glycolysis, and glycogen synthesis and the rates of 2-deoxyglucose uptake in individual tissues were similar in Leptin - and Leptin +. Post-absorptive hepatic glucose production (HGP) was similar in the two groups. However, leptin enhanced insulin's inhibition of HGP (4.1 +/- 0.7 and 6.2 +/- 0.7 mg/kg.min; p < 0.05). The decreased HGP in the Leptin + group was due to a marked suppression of hepatic glycogenolysis (0.7 +/- 0.1 versus 4.1 +/- 0.6 mg/kg.min, in Leptin + versus Leptin -, respectively; p < 0.001), whereas the % contribution of gluconeogenesis to HGP was markedly increased (82 +/- 3% versus 36 +/- 4% in Leptin + and Leptin -, respectively; p < 0.001). At the end of the 6-h leptin infusion, the hepatic abundance of glucokinase mRNA was decreased, whereas that of phosphoenolpyruvate carboxykinase mRNA was increased compared with Leptin -. We conclude that an acute increase in plasma leptin 1) enhances insulin's ability to inhibit HGP, 2) does not affect peripheral insulin action, and 3) induces a redistribution of intrahepatic glucose fluxes and changes in the gene expression of hepatic enzymes that closely resemble those of fasting.

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Authors: Rossetti, L., Massillon, D., Barzilai, N., Vuguin, P., Chen, W., Hawkins, M., Wu, J., & Wang, J.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Rossetti, Luciano
ORCID: Rossetti, Luciano
Barzilai, Nir
Vuguin, Patricia
Chen, Wei
Hawkins, Meredith
Wu, Jie
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1997-10
Volume: 272
Issue: 44
Pages: 27758-27763
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.272.44.27758
OpenAlex: W2085529816
Cited by: 304
References: 38
Citations by year: 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 11 · 2012: 15
FWCI: 6.00
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, 8416 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Amgen
National Institutes of Health
Albert Einstein College of Medicine, Yeshiva University
National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, DK-45024)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: leptin, hepatic gluconeogenesis, insulin action, hepatic glucose production, hepatic glycogenolysis, insulin sensitivity, glucokinase, phosphoenolpyruvate carboxykinase, hepatic gene expression, glucose metabolism, fasting
MeSH terms: Animals, Deoxyglucose, Glucokinase, Gluconeogenesis, Hyperinsulinism, Insulin, Liver Glycogen, Male, Proteins, RNA, Messenger, Rats, Sprague-Dawley, Patch-Clamp Techniques, Phosphoenolpyruvate Carboxykinase (ATP), Leptin, Rats

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Short Term Effects of Leptin on Hepatic Gluconeogenesis and in Vivo Insulin Action

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