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  Franšais - August 16, 2011
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 Presentation

"How does insulin regulate gene expression in health and disease ?"

Dr. Phillip Marsden (biography)
English - 2003-03-28 - 44 minutes
(33 slides)
(1 question)

Summary :
Newer insights are emerging with respect to how insulin, the key anabolic hormone, modulates gene expression in health. Insulin controls the amount of key proteins through actions that affect steady-state levels of mRNA, through direct effects on transcription of the gene or indirectly through effects on genral modifiers of transcription. Perturbations in the processes that mediate insulin-induced gene expression are directly relevant to disease. Through the study of specific genes, greater insight is emerging into how insulin controls gene transcription. A model that illustrates the complexities, as well as the finesse, involved in how insulin regulates gene expression is the sterol response element binding protein (SREBP). Mutations in the transcription factor PPAR gamma are associated with severe insulin resistance and represent a genetic susceptibility locus for human diabetes. Little is known about the transcriptional changes induced in vivo by insulin in human tissues. A newer approach to this question has exploited the use of cDNA microarray technologies to gain insight into the specific genes, or classes of genes, that are affected by insulin. Innovative studies have assessed this question using short-term euglycemic insulin clamps and biopsies of human skeletal muscle. This methodology has also been used to study the effects of insulin treatment in animal models of diabetes and type 2 diabetic patients.

Learning objectives :
Importantly, insulin controls the amount of key proteins by modifying the efficiency of mRNA translation. This review provides examples of the relevance of the insulin-induced changes in the mRNA translational process in health and disease.

Bibliographic references :
http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=12618528

J Clin Invest 2003 Mar;111(5):737-47
Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes.

Matsusue K, Haluzik M, Lambert G, Yim SH, Gavrilova O, Ward JM, Brewer B Jr, Reitman ML, Gonzalez FJ.

   


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