| Autor: |
Mads Kjolby, Peter Breining, Karen Pedersen, Niels Wellner, Karen Sørensen, Anette Gjessing, Dovile Januliene, Dorthe Vittrup, Arulmani Manavalan, Maarten Rotman, Gangadaar Thotakura, Guido Hermey, Peder Madsen, Christian Vaegter, Søren Thirup, Olof Asplund, Rashmi Prasad, Edwin Parlevliet, Patrick Rensen, Andreas Madsen, Birgitte Holst, Olav Andersen, Arne Moller, Torben Hansen, Anders Nykjaer |
| Rok vydání: |
2022 |
| Popis: |
Type 2 diabetes has reached endemic proportions and is a substantial burden for the affected patients and the society. Along with lifestyle factors, a number of genetic loci predisposing to type 2 diabetes have been identified, including SORCS1 that encodes the transmembrane receptor SorCS1. The ectodomain of SorCS1 (sol-SorCS1) is shed from plasma membranes but the biological function of this fragment is unknown. Here we show that sol-SorCS1 acts as a high-affinity binding partner for the insulin receptor to stabilize the receptor and increase insulin affinity, protein kinase B activation, and glucose uptake in myocytes. Sol-SorCS1 is liberated from adipocytes, and in diabetic patients the plasma concentration positively correlates with body mass index, but inversely with plasma glucose. In mouse models of insulin resistance, exogenous sol-SorCS1 restored insulin sensitivity. We conclude that sol-SorCS1 increases peripheral insulin sensitivity and propose sol-SorCS1 as a novel insulin sensitizing adipokine and potential antidiabetic agent. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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