Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle

Institut National de la Santé et de la Recherche Médicale U 449, Faculté de Médecine Alexis Carrel, Lyon, France.
Journal of Clinical Investigation (Impact Factor: 13.22). 08/1996; 98(1):43-9. DOI: 10.1172/JCI118775
Source: PubMed


We have investigated the acute regulation by insulin of the mRNA levels of nine genes involved in insulin action, in muscle biopsies obtained before and at the end of a 3-h euglycemic hyperinsulinemic clamp. Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. The relative expression of the two insulin receptor variants was not modified. These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin.

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Available from: Martine Laville, Feb 09, 2015
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    • "Investigations were performed after an overnight fast. Insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp as previously described (13), with a 1 mUI ⋅ kg−1 ⋅ min−1 insulin infusion for 120 min. Glucose infusion rate (GIR) was calculated during the final 30 min of the clamp. "
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    • "Although PI3K is a key regulator of insulin signaling, surprisingly, little is known about the signaling mechanisms that modulate the expression of the regulatory subunits of PI3K in response to nutrient flux. Increased expression of p85α in peripheral tissues occurs in response to increased insulin (40), growth hormone (21), and dexamethasone (41). Additionally, rosiglitazone increases p85α expression in human adipocytes through peroxisome proliferator–activated receptor γ activation (42), and SkM p85α expression is strongly induced by peroxisome proliferator–activated receptor α activation (43). "
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