Extracellular Signal-regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-induced Glucose Uptake in Red-type Skeletal Muscle

Overview

Journal Diabetes

Specialty Endocrinology

Date 2013 Mar 27

PMID 23530005

Citations 34

Authors

Chitoku Toda

Tetsuya Shiuchi

Haruaki Kageyama

Shiki Okamoto

Eulalia A Coutinho

Tatsuya Sato

Yuko Okamatsu-Ogura

Shigefumi Yokota

Kazuyo Takagi

Lijun Tang

Kumiko Saito

Seiji Shioda

Yasuhiko Minokoshi

Affiliations

Soon will be listed here.

Abstract

Leptin is a key regulator of glucose metabolism in mammals, but the mechanisms of its action have remained elusive. We now show that signaling by extracellular signal-regulated kinase (ERK) and its upstream kinase MEK in the ventromedial hypothalamus (VMH) mediates the leptin-induced increase in glucose utilization as well as its insulin sensitivity in the whole body and in red-type skeletal muscle of mice through activation of the melanocortin receptor (MCR) in the VMH. In contrast, activation of signal transducer and activator of transcription 3 (STAT3), but not the MEK-ERK pathway, in the VMH by leptin enhances the insulin-induced suppression of endogenous glucose production in an MCR-independent manner, with this effect of leptin occurring only in the presence of an increased plasma concentration of insulin. Given that leptin requires 6 h to increase muscle glucose uptake, the transient activation of the MEK-ERK pathway in the VMH by leptin may play a role in the induction of synaptic plasticity in the VMH, resulting in the enhancement of MCR signaling in the nucleus and leading to an increase in insulin sensitivity in red-type muscle.

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