A double negative: Inhibition of hepatic gi signaling improves glucose homeostasis

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)567-569
Number of pages3
JournalJournal of Clinical Investigation
Issue number2
StatePublished - Feb 1 2018

ASJC Scopus subject areas

  • Medicine(all)


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