Role of AMPK and LKB1 in contraction and exercise induced muscle glucose uptake
PhD thesis by Stine Just Maarbjerg
2011, 155 pages, DKR 100,-
ISBN: 978 87 917 7136 1
Physical exercise plays an important role in prevention and treatment of type 2 diabetes
In response to physical exercise glucose uptake increases markedly in the active muscles. Importantly this ability to increase glucose uptake during muscle contractions is preserved in people with insulin resistance and type 2 diabetes, which are both characterized by impaired insulin stimulated muscle glucose uptake. Consequently the mechanisms responsible for contraction and exercise induced muscle glucose uptake are potential therapeutic targets regarding the ever increasing number of people with type 2 diabetes worldwide.
Increase in AMP-activated protein kinase (AMPK) activity is causally linked to muscle glucose uptake in response to treatment with the pharmacological agent AICAR. As muscle AMPK activity, similar to muscle glucose uptake, increases in an intensity dependent manner, it was been hypothesis that AMPK is responsible for the increase in glucose uptake during muscle contractions.
The present PhD thesis provides a review regarding the current understanding of AMPK and the upstream kinase of AMPK, LKB1, in regulation of muscle glucose metabolism. In three studies using three different transgenic mouse models to impair AMPK signaling, this thesis explores the role of AMPK and LKB1 in muscle glucose uptake during contraction and physiological exercise in mice. The results obtained in the three studies are finally discussed in context with the recent progress in the field of AMPK and LKB1 in regulating muscle glucose uptake.
Contents (pdf, 213 kb)
Summary (pdf, 242 kb)
List of manuscripts (pdf, 106 kb)