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

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

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

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,

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.

Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. Publishing Authors By Initials

VT Samuel,ZX Liu,A Wang,SA Beddow,JG Geisler,M Kahn,XM Zhang,BP Monia,S Bhanot,GI Shulman,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 739-45

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 22

MONTH: 02

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: agonists

Chemical & Substance for Abstract: Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. Information

Substance Name: Protein Kinase C-epsilon

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease.

AFFILIATION: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R01 DK40936

ACRONYM: DK

MEDLINETA: J Clin Invest

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