Novel protein networks regulating glucose transport and glycogen synthesis

Novel protein networks regulating glucose transport and glycogen synthesis -
13.11.17

In a new article published in Molecular & Cellular Proteomics (October 2017), Danish Diabetes Academy Post Doc Rikke Kruse and Professor Kurt Højlund, in collaboration with researchers from Arizona State University, characterized the CLASP2 protein interaction network. The collaboration was established when Rikke Kruse visited Dr. Langlais at Mayo Clinic, Phoenix, Arizona as part of her PhD.

A NOVEL REGULATOR OF INSULIN-STIMULATED GLUCOSE UPTAKE

Insulin resistance, defined as reduced insulin-stimulated glucose disposal in skeletal muscle and fat, is a major hallmark of type 2 diabetes. The mechanisms underlying insulin resistance involve impaired glucose uptake through the insulin-sensitive glucose transporter GLUT4 and reduced glucose synthesis due to attenuated activation of glycogen synthase. Recent work from Langlais P et al. has demonstrated an important role for the microtubule-associated protein CLASP2 in insulin-mediated GLUT4 translocation to the plasma membrane, and hence glucose transport.

MAPPING OF A CLASP2 PROTEIN NETWORKS ASSOCIATED WITH INSULIN ACTION

The aim of the current study was to gain further insight into the role of CLASP2 in glucose transport using a mass spectrometry-based interactome approach to build the CLASP2 protein networks in 3T3-L1 adipocytes. Interestingly, we found CLASP2 to interact with SOGA1 and MARK2, which both showed association with glycogenin and glycogen synthase. The results demonstrate a role for CLASP2 protein networks not only on insulin-mediated on glucose transport, but possible also on insulin action on glycogen synthesis, which is a defect commonly observed in type 2 diabetes. A figure showing the proposed CLASP2 network model and its relation to insulin-stimulated glucose uptake and glucose storage covers the front-page of the October issue of Molecular & Cellular Proteomics.

The discovery of these new CLASP2 protein networks suggests a functional association between microtubule dynamics, actin reorganization, and insulin action on glucose uptake and storage. These findings may contribute to an increased insight into the development of insulin resistance and could provide novel targets for prevention and treatment of type 2 diabetes.

AUTHORS AND AFFILIATIONS

Kruse R, Krantz J, Barker N, Coletta R, Rafikov R, Luo M, Hoejlund K, Mandarino LJ, Langlais PR.

Source: Molecular & Cellular Proteomics