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IS-DAAD-Forskerutveksl. Norge-Tyskland

Insulin signaling pathways in skeletal muscle

Tildelt: kr 87 062

Type 2 diabetes is associated with insulin resistance in skeletal muscle, in which the transmission of signals within the cells is impaired. This results in an aberrant glucose and lipid metabolism that negatively impacts whole body glycemic control. Importantly, alterations in insulin signaling can be detected very early on in the development of the disease, even in the absence of clinical phenotypes, implicating a causative role of muscle insulin resistance in the onset of diabetes. The signal transmission of insulin is based on a cascade-like, rapid and reversible phosphorylation of proteins in which, in the end, specific effectors, enzymes and transcription factors are activated or inhibited. Both contraction and insulin stimulation result in increased glucose uptake and are thought to share common signaling pathways in skeletal muscle. It is currently unknown at which point the pathways converge, and where impairments in signal transduction occur in the insulin-resistant state. Insulin-dependent signaling pathways in cultured skeletal muscle cells of metabolically healthy individuals and individuals with T2D are studied using quantitative metabolic measurements and high-resolution mass spectroscopy. In addition, the cultured skeletal muscle cells will be exposed to a model of in vitro exercise (electrical pulse stimulation, EPS), and potential antidiabetic drugs targeting skeletal muscle. Signal transduction is investigated with the help of mass spectroscopy through time and dose-dependent measurements of the global phosphoproteome. The aim is to investigate how and at what level the signaling cascade is altered or interrupted in diabetes, and if and how this can be counteracted by exercise and/or pharmacological agents. Also metabolic characteristics of the cells will be measured.


IS-DAAD-Forskerutveksl. Norge-Tyskland