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Title: | Increased hepatic insulin sensitivity in mice lacking inhibitory leptin receptor signals |
Author: | Tom, Robby Zachariah Sjögren, Rasmus J. O. Vieira, Elaine Glund, Stephan Iglesias-Gutiérrez, Eduardo García-Roves, Pablo M. (Pablo Miguel) Myers Jr, Martin G. Björnholm, Marie |
Keywords: | Insulina Malalties del fetge Leptina Ratolins (Animals de laboratori) Insulin Liver diseases Leptin Mice (Laboratory animals) |
Issue Date: | 1-Jun-2011 |
Publisher: | Association for the Study of Internal Secretions |
Abstract: | Leptin regulates food intake and energy expenditure by activating the long form of the leptin receptor (LepRb). Leptin also regulates glucose homeostasis by improving whole-body insulin sensitivity, but the mechanism remains undefined. Leptin action is mediated by phosphorylation of several tyrosine residues on LepRb. LepRb-Tyr985 plays an important role in the attenuation of LepRb signaling. We determined the contribution of LepRb-Tyr985-mediated signals to leptin action on insulin sensitivity using LepRb-Tyr985 mutant mice (l/l mice). Glucose tolerance and whole-body insulin-mediated glucose utilization were determined in wild-type (+/+) and l/l mice. Glucose tolerance was unaltered between female +/+ and l/l mice but enhanced in the male l/l mice. Serum insulin concentration was decreased at baseline and 15 min after a glucose injection in female l/l vs. +/+ mice (P < 0.05) but unaltered in the male l/l mice. However, basal and insulin-stimulated glucose transport in isolated soleus and extensor digitorum longus muscle was similar between +/+ and l/l mice, indicating skeletal muscle insulin sensitivity in vitro was not enhanced. Moreover, euglycemic-hyperinsulinemic clamps reveal hepatic, rather than peripheral, insulin sensitivity is enhanced in female l/l mice, whereas male l/l mice display both improved hepatic and peripheral insulin sensitivity. In conclusion, signals emanating from leptin receptor Tyr985 control hepatic insulin sensitivity in both female and male l/l mice. Lack of LepRb-Tyr985 signaling enhances whole-body insulin sensitivity partly through increased insulin action on the suppression of hepatic glucose production. |
Note: | Reproducció del document publicat a: https://doi.org/10.1210/en.2010-0040 |
It is part of: | Endocrinology, 2011, vol. 152, num. 6, p. 2237-2246 |
URI: | http://hdl.handle.net/2445/134420 |
Related resource: | https://doi.org/10.1210/en.2010-0040 |
ISSN: | 0013-7227 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) |
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