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Upregulation of Protein Kinase C‐ζ Gene and Protein Expression by Exercise Training in Muscle of Obese Zucker Rats: Correlation with Enhanced Glucose Tolerance
Author(s) -
Henriksen Erik J.,
Ort Tatiana,
Lindborg Katherine A.,
Gerwien Robert,
Diehl Cody J.,
Lemieux Andrew M.,
Eisen Andrew
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a576-d
Subject(s) - medicine , endocrinology , downregulation and upregulation , skeletal muscle , insulin resistance , type 2 diabetes , protein kinase c , gene expression , insulin , soleus muscle , glucose tolerance test , diabetes mellitus , biology , gene , kinase , microbiology and biotechnology , biochemistry
Exercise training decreases skeletal muscle insulin resistance and increases glucose tolerance in conditions of pre‐diabetes. However, the relevant adaptive responses at the molecular and genetic level have not been clearly established in an animal model of pre‐diabetes. This study identifies novel alterations in muscle gene and protein expression that occur with exercise training in pre‐diabetic obese Zucker rats and are associated with a well‐defined metabolic outcome. Treadmill running (1–4 wks) enhanced glucose tolerance as assessed by the area under the curve for glucose (AUCg) during a glucose tolerance test. Microarray analysis revealed that a limited set of genes in soleus muscle was both significantly altered by exercise training (>1.5‐fold change; p<0.05) and correlated (p<0.05) with AUCg. One of these genes was the ζ‐isoform of protein kinase C (PKC‐ζ), a distal element of the insulin signaling pathway. PKC‐ζ protein expression was also upregulated (39%, p<0.05) by exercise training and was positively correlated with both its mRNA expression level and with AUCg. We provide the first evidence that PKC‐ζ gene and protein expression are enhanced by exercise training in skeletal muscle from an obesity‐associated rat model of insulin resistance. Moreover, this study presents the novel finding that the exercise training‐induced upregulation of PKC‐ζ expression in soleus muscle of obese Zucker rats is associated with increased glucose tolerance. PKC‐ζ should be targeted for the development of pharmaceutical “exercise mimetics” in the treatment of insulin‐resistant pre‐diabetic or overtly type 2 diabetic individuals.