RGD Reference Report - Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. - Rat Genome Database

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

Authors: Samuel, VT  Liu, ZX  Wang, A  Beddow, SA  Geisler, JG  Kahn, M  Zhang, XM  Monia, BP  Bhanot, S  Shulman, GI 
Citation: Samuel VT, etal., J Clin Invest. 2007 Mar;117(3):739-45. Epub 2007 Feb 22.
RGD ID: 2307035
Pubmed: PMID:17318260   (View Abstract at PubMed)
PMCID: PMC1797607   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI30400   (Journal Full-text)

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, PKCepsilon, but not other isoforms of PKC, is activated. To determine whether PKCepsilon plays a causal role in the pathogenesis of hepatic insulin resistance, we treated rats with an antisense oligonucleotide against PKCepsilon and subjected them to 3 days of high-fat feeding. Knocking down PKCepsilon expression protects rats from fat-induced hepatic insulin resistance and reverses fat-induced defects in hepatic insulin signaling. Furthermore, we show that PKCepsilon 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 PKCepsilon plays a critical role in mediating fat-induced hepatic insulin resistance and represents a novel therapeutic target for type 2 diabetes.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein kinase binding  IPIPrkce (Rattus norvegicus)2307035 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)


Additional Information