The role of PRAS40 in insulin action : at the intersection of protein kinase B (PKB/Akt) and mamalian target of rapamyein (mTOR)

Nascimento, E.B.M. (2010)

Doctoral Thesis

Diabetes is taking on epidemic proportions, not only in western society. Via the blood, glucose is transported to the organs in the human body. When a meal is consumed, blood glucose levels rise. Insulin is secreted from the pancreas in response to the increased blood glucose levels and lowers blood glucose by increasing glucose uptake in insulin-sensitive tissues. Under conditions of insulin resistance, insulin does not have its full effect resulting in increased blood glucose levels, which left untreated will result in diabetes. Also at the signal transduction level insulin resistance is evident. An important signaling intermediate is protein kinase B (PKB/Akt). Its activity is decreased under conditions of insulin resistance. However PKB/Akt phosphorylates many targets and not all phosphorylation targets have been linked to a specific function. Therefore the aim of the research conducted in the thesis was to examine the role of PKB/Akt phosphorylation target PRAS40 in insulin action. PRAS40 is expressed in insulin sensitive tissues and is phosphorylated in response to insulin. PRAS40 interacts with another component of the insulin signaling cascade: mammalian target of rapamycin. Under conditions of insulin resistance, PRAS40 phosphorylation is decreased and higher expression of PRAS40 has a protective role in insulin resistance.

• Diabetes
• Insulin action
• Mammalian target of rapamycin
• PRAS40
• Protein kinase B
• Signal transduction

• All authors: Nascimento, E.B.M.
• Supervisor: Dijke, P. ten; Maassen, J.A.
• Co-supervisor: Ouwens, D.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2010-09-09
• ISBN (print): 9789461080622
• Sponsorship: Nederlands diabetesfonds