Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells.

Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Research Abstract Details 

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Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Abstract Text:

Theodore P Ciaraldi,Svetlana E Nikoulina,Rahil A Bandukwala,Leslie Carter,Robert R Henry,

An association between glycogen synthase kinase-3 (GSK3) in skeletal muscle and insulin resistance has been demonstrated in type 2 diabetic patients. In addition, inhibition of GSK3 improves insulin action. The aim of the present study was to elucidate the role of the alpha-isoform of GSK3 in insulin resistance in human skeletal muscle cells from nondiabetic subjects maintained in culture. Transfection of muscle cells with specific antisense oligonucleotides resulted in a 30-50% decrease of GSK3alpha protein expression (P < 0.05). Whereas neither the basal fractional velocity of glycogen synthase (GS FV) (an indicator of the activation state of the enzyme) nor glucose uptake (GU) were altered, reducing GSK3alpha expression resulted in increases in insulin stimulation of both GS FV and GU. GSK3alpha overexpression (60-100% increase over control) did not alter basal GS FV or GU but impaired insulin stimulation of both responses. Knockdown of GSK alpha also led to an increase in insulin receptor substrate-1 protein expression but did not alter insulin stimulation of pS473-Akt phosphorylation. However, GSK3alpha overexpression impaired insulin action on pS473-Akt. In summary, we concluded the following: 1) modulation of GSK3alpha expression has no effect on basal GU and glycogen synthase activities; 2) reduction of GSK3alpha expression results in improvements in insulin action; and 3) elevation of GSK3alpha in human skeletal muscle cells can induce insulin resistance for several responses. We conclude that GSK3alpha is an important regulator of muscle insulin action.

Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Publishing Authors By Initials

TP Ciaraldi,SE Nikoulina,RA Bandukwala,L Carter,RR Henry,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Journal Published:

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

Journal: Endocrinology

VOLUME: 148

Page Numbers: 4393-9

Journal Abbreviation: Endocrinology

ISSN: 0013-7227

DAY: 14

MONTH: 06

YEAR: 2007

Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 375040

Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: enzymology

Chemical & Substance for Abstract: Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells. Information

Substance Name: glycogen synthase kinase 3 alpha

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Role of glycogen synthase kinase-3 alpha in insulin action in cultured human skeletal muscle cells.

AFFILIATION: Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, California 92161, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R01-DK-258291

ACRONYM: DK

MEDLINETA: Endocrinology

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