A double negative: inhibition of hepatic G<sub>i</sub> signaling improves glucose homeostasis

Allen M. Spiegel

doi:10.1172/JCI99037

A double negative: inhibition of hepatic G_i signaling improves glucose homeostasis

Department of Medicine, Division of Endocrinology and Diabetes, and Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.

Address correspondence to: Allen M. Spiegel, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 312, Bronx, New York 10461, USA. Phone: 718.430.2801; Email: allen.spiegel@einstein.yu.edu.

Find articles by Spiegel, A. in: JCI | PubMed | Google Scholar

First published January 16, 2018 - More info

Published in Volume 128, Issue 2 on February 1, 2018
J Clin Invest. 2018;128(2):567–569. https://doi.org/10.1172/JCI99037.
Copyright © 2018, American Society for Clinical Investigation

First published January 16, 2018 - Version history

Hepatic glucose production (HGP) is a key determinant of glucose homeostasis. Glucagon binding to its cognate seven-transmembrane Gs-coupled receptor in hepatocytes stimulates cAMP production, resulting in increased HGP. In this issue of the JCI, Rossi and colleagues tested the hypothesis that activation of hepatic Gi–coupled receptors, which should inhibit cAMP production, would oppose the cAMP-inducing action of glucagon and thereby decrease HGP. Surprisingly, however, the opposite occurred: activation of Gi signaling increased HGP via a novel mechanism, while inhibition of Gi signaling reduced HGP. These results define a new physiologic role for hepatic Gi signaling and identify a potential therapeutic target for HGP regulation.

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A double negative: inhibition of hepatic Gi signaling improves glucose homeostasis

Allen M. Spiegel