Lund University is celebrating 350 years. Read more on lunduniversity.lu.se

Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

Islet patophysiology

Department of Clinical Sciences Malmö
Head: Erik Renström

Ion channels play overarching roles as sensors of cellular activity and control long-term adaptation of the endocrine pancreatic islet to the environmental demands. Certain ion channel subunits directly act as transcription factors. Furthermore, changes in intracellular ion homeostasis control gene expression, catalyze posttranslational modifications and change the pattern of signaling molecules and metabolites. In fact, the acute control of cellular excitability and hormone secretion represents only part of ion channel functions in e.g. the beta-cell. For example, beta-cell ion channels, control insulin content, beta-cell survival, beta-cell differentiation status and are affect beta-cell  pathophysiology and diabetes development in ways previously  poorly recognized.
Ion channel function is enhanced by their clustering into hot spots. Ion channel subunits, GPCRs, membrane lipids as well as GPI-linked plasma membrane proteins such cluster formations.
Ion channels sensitive to different modalities – voltage, particular ligands, mechanical/osmotic  stimulus are specifically expressed in different islet cell types.
Superparamegnetic nanoparticles in combination with magnetic field generation offers the possibility for controlled receptor activation and mechanical stimulation.

Goals

Signals involved in cellular responses to beta-cell overload

  • Role of voltage-gated Ca2+ channel subunits and Ca2+ signals for beta-cell gene expression, differentiation status, secretory capacity and diabetes
  • Role of non-voltage-gated  ion channels and ligands and mechanical signals for beta-cell gene expression, differentiation status, secretory capacity and diabetes

Novel therapeutic approaches

  • Superparamagnetic nanoparticles as tools for targeted receptor activation and triggering of mechanosensing         

Impact

Identify disease-modifying mechanisms that protect endogenous insulin release and diabetes development

Highlights

2015: The Knud Lundbeck Award, presented by the Scandinavian Society for the Study of Diabetes
2014: Krus, U, King, BC, Nagaraj, V, Gandasi, NR,  Sjölander, J,  Buda, P, Garcia-Vaz, E, Gomez, MF, Ottosson–Laakso, E, Storm, P, Fex, M, Vikman, P, Zhang, E, Barg, S, Blom, AM, Renström, E.  The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events Cell Metabolism 19(5):883–890
2014: Zhang E, Kircher MF, Koch M, Eliasson L, Goldberg SN, Renström E. Dynamic Magnetic Fields Remote Control Apoptosis Via Nanoparticle Rotation  ACS Nano 8(4):3192–3201
2010: Rosengren, A.H., Jokubka, R., Tojjar, D., Granhall, C., Hansson, O., Li, D-Q., Nagaraj, V., Reinbothe, T.M., Tuncel, J., Eliasson, L., Groop, L., Rorsman, P.,  Salehi, S.A., Lyssenko, V., Luthman, H., Renström, E. Overexpression of alpha2A adrenergic receptors contributes to type 2-diabetes. Science 327(5962):217-20. Epub 2009 Nov 19.
2009: Li, D-Q., Jing, X., Salehi, S.A., Collins, S.C., Hoppa, M.B., Rosengren, A.H., Zhang, E., Lundquist, I., Olofsson, C.S., Mörgelin, M., Eliasson, L., Rorsman, P., Renström, E.

 Suppression of sulfonylurea- and glucose-induced insulin secretion in vitro and in vivo in mice lacking the chloride transport protein ClC‑3 (2009) Cell Metabolism 10(4):309-315

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00