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Short Term Effects of Leptin on Hepatic Gluconeogenesis and in Vivo Insulin Action
Open accessAbstract
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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“This enhanced insulin-mediated suppression of glucose production was due to a marked suppression of hepatic glycogenolysis, whereas gluconeogenesis was paradoxically increased (152).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [152]
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“In non-diabetic rats, an acute intravenous (i.v.) leptin infusion enhanced insulin's ability to suppress glucose production without affecting glucose uptake.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [152]
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Metadata
- 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
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 272
- Issue
- 44
- Pages
- 27758-27763
- ISSN
- 0021-9258 (ISSN-L)
- 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
- 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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