Bengtsson, Tore (Physiology (Wenner-Gren Institute)) http://su.avedas.com/converis/ws/public/feed/simple/atom/Person/231/Contract 2013-05-16T02:02:22Z 2013-05-16T02:02:22Z Tore Bengtsson http://su.avedas.com/converis/contract/2303 2012-12-18T14:20:40Z 2010-05-22T02:01:59Z

Transmission of a signal across the plasma membrane is a fundamental cellular process. G-protein coupled receptors (GPCRs) are the largest class of cell surface receptors and are thus important players in this essential task. GPCRs are also the targets for more than 50 percent of all current therapeutic agents. Adrenergic receptors (ARs) are prototypical GPCRs that are activated by the endogenous hormones noradrenaline and adrenaline and involved in the regulation of virtually every organ system in the body. To understand through which mechanisms GPCRs signal into the cell and how the signal is turned off is of high importance. We believe we have found evidence for adrenergic receptor signal switching, where adrenergic receptors first couple to “classical” second messengers, are desensitized and then as a third event switches signaling pathway. This leads to activation of a molecule (PI3K) which is normally associated with the insulin signaling pathway. Signaling switching may be a paradigmatic event which occurs for all GPCRs. In this application we want to molecularly investigate the mechanism of the adrenergic receptor signal switching to PI3K. We also want to investigate if adrenergic signal switching leads to important biological end points such as regulation of glucose uptake. The long term vision is to understand if signal switching is a fundamental process of GPCRs.

Tore Bengtsson 2010-05-22T02:01:59Z Tore Bengtsson http://su.avedas.com/converis/contract/2356 2012-12-18T14:20:42Z 2010-05-22T02:02:01Z

Obesity is a major inducer of type 2 diabetes and more than 150 million people worldwide suffer from type 2 diabetes. Stress has been proposed as one potential contributor to Type II diabetes but there are surprisingly few studies on this topic. Most attempts to treat type 2 diabetes have focused on improving insulin signaling. However, lately, great interest has developed in identifying insulin-independent mechanisms in order to find new treatments. We have found compelling evidence that activation of adrenergic receptors lead to an insulin-independent mechanism that increases glucose uptake in skeletal muscle. We have found that stimulation of beta2-AR in muscle, in addition to increasing cAMP levels, also activates PI3K (an important kinase normally associated with insulin-signaling) via an unknown mechanism. The beta-adrenergic activation of PI3K in skeletal muscle cells leads to an increase in glucose uptake of the same magnitude as the one mediated by insulin (but probably not through the same glucose transporters). In this application we want to investigate the signaling proteins and mechanisms of action used by adrenergic receptors to activate glucose uptake in muscle cells. It is of considerable importance to understand how adrenergic signaling leads to glucose uptake and the interplay between the insulin and adrenergic pathways. This can have great impact on our understanding and development of potential new treatments of type 2 diabetes.

Tore Bengtsson 2010-05-22T02:02:01Z Tore Bengtsson http://su.avedas.com/converis/contract/4623 2013-05-16T02:02:21Z 2011-09-15T02:00:55Z Tore Bengtsson 2011-09-15T02:00:55Z Tore Bengtsson http://su.avedas.com/converis/contract/4860 2013-05-16T02:02:21Z 2011-12-18T02:19:48Z Tore Bengtsson 2011-12-18T02:19:48Z