Submit a comment

Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease
Varman T. Samuel, Zhen-Xiang Liu, Amy Wang, Sara A. Beddow, John G. Geisler, Mario Kahn, Xian-man Zhang, Brett P. Monia, Sanjay Bhanot, Gerald I. Shulman
Varman T. Samuel, Zhen-Xiang Liu, Amy Wang, Sara A. Beddow, John G. Geisler, Mario Kahn, Xian-man Zhang, Brett P. Monia, Sanjay Bhanot, Gerald I. Shulman
View: Text | PDF
Research Article Metabolism

Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease is strongly associated with hepatic insulin resistance and type 2 diabetes mellitus, but the molecular signals linking hepatic fat accumulation to hepatic insulin resistance are unknown. Three days of high-fat feeding in rats results specifically in hepatic steatosis and hepatic insulin resistance. In this setting, PKCε, but not other isoforms of PKC, is activated. To determine whether PKCε plays a causal role in the pathogenesis of hepatic insulin resistance, we treated rats with an antisense oligonucleotide against PKCε and subjected them to 3 days of high-fat feeding. Knocking down PKCε expression protects rats from fat-induced hepatic insulin resistance and reverses fat-induced defects in hepatic insulin signaling. Furthermore, we show that PKCε associates with the insulin receptor in vivo and impairs insulin receptor kinase activity both in vivo and in vitro. These data support the hypothesis that PKCε plays a critical role in mediating fat-induced hepatic insulin resistance and represents a novel therapeutic target for type 2 diabetes.

Authors

Varman T. Samuel, Zhen-Xiang Liu, Amy Wang, Sara A. Beddow, John G. Geisler, Mario Kahn, Xian-man Zhang, Brett P. Monia, Sanjay Bhanot, Gerald I. Shulman

×

Guidelines

The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.

  • Comments appear on the Journal’s website and are linked from the original article’s web page.
  • Authors are notified by email if their comments are posted.
  • The Journal reserves the right to edit comments for length and clarity.
  • No appeals will be considered.
  • Comments are not indexed in PubMed.

Specific requirements

  • Maximum length, 400 words
  • Entered as plain text or HTML
  • Author’s name and email address, to be posted with the comment
  • Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
  • Comments may not include figures
This field is required
This field is required
This field is required
This field is required
This field is required
This field is required