Alternative β-adrenergic signaling: an innovative way to treat type II diabetes


Project leader


Funding source

Swedish Research Council - Vetenskapsrådet (VR)


Project Details

Start date: 01/01/2016
End date: 31/12/2019
Funding: 4000000 SEK


Description

We have discovered a physiological pathway, leading to glucose uptake, that we believe can be used to treat type II diabetes. The pathway works independently of insulin and is reliant on stimulation of adrenergic receptors (AR) resulting in increased glucose uptake in skeletal muscle and brown fat in rodent and human model systems. In this application, we put forward a novel and exciting hypothesis that this pathway can be utilized to treat type II diabetes in humans without the usual adrenergic side effects, such as tremor, palpitation and anxiety. We therefore aim to I) fully characterize this novel molecular pathway, II) study the effects of the pathway in-vivo and III) examine if this pathway, and ligands that activate it, can be used to treat type II diabetes. Initially we will dissect the molecular pathway in vitro with cutting edge pharmacology, molecular and genetic tools, including light-inducible nuclear localization signals (LINuS) and state-of-the-art microscopy, including total internal reflection fluorescence (TIRF) and 2-photon excitation methods. These sophisticated techniques, combined with positron emission tomography (PET), will be utilized for the first time in vivo to scrutinize the effect of the physiological pathway in healthy and diabetic model systems. We have recently developed novel β-AR ligands that enable us to specifically and selectively activate glucose uptake via this pathway. Our exciting preliminary data show improved glucose clearance after long-term treatment with one of these ligands in a type II diabetes model. Therefore, these ligands are exceptional tools, giving us a unique opportunity to further explore this signaling pathway in mammals and, moreover, potentially to develop a new, effective drug for type II diabetes. Our research will not only advance current knowledge of β-adrenergic signaling but also provide the basis for a novel, previously inconceivable, treatment that can propel the type II diabetes field fundamentally forward, with significant impact on the health system and patient wellbeing.


Last updated on 2017-01-06 at 11:44