Effects of diabetes related-genes on beta cell function and organism physiology

  

Our work makes use of zebrafish diabetes models, as well as novel in vivo imaging modalities, to investigate the following:

  • Image-effects1 Requirement for diabetes-associated ion-channels in glucose-induced beta-cell excitability. We are also interested in the role of signaling between islet cell subtypes in maintaining glucose homeostasis, and changes that occur in diabetes.
  •  Long term impact of disrupted glucose homeostasis. We use zebrafish diabetes models to investigate tissue-specific changes in glucose transport and metabolism in susceptible tissues, and to define molecular mechanisms of organ pathologies.
  •  Metabolic response of beta cells to sustained glucose elevation. Our group is exploring how hyperglycemia induces oxidative stress and mitochondrial changes, leading to disruption of beta cell function and decreased survival.

 

Project Team: Robin Kimmel, Dirk Meyer, Nicole Schmitner, Andrea Figer, Ferdinand Löffler

Featured in BPOD (Biomedical Picture of the Day):

Zebrafish Model of Diabetic Retinopathy

 

Selected Publications

Schmitner, N., Recheis, C., Thönig, J., Kimmel, R.A. (2021) Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia. Cells, 10, 3265. FEBS Letters Volume 597, Issue 2; January 2023; Pages 262-275. https://doi.org/10.3390/cells10113265

Ali Z, Zang J, Lagali N, Schmitner N, Salvenmoser W, Mukwaya A, Neuhauss S, Jensen L and Kimmel RA. Photoreceptor degeneration accompanies vascular changes in a zebrafish model of diabetic retinopathy. Investigative Ophthalmology & Visual Science. February 2020, Vol.61, 43. doi:https://doi.org/10.1167/iovs.61.2.43

Emfinger CH, Lőrincz R, Wang Y, York NW, Singareddy SS, Ikle JM, Tryon RC, McClenaghan C, Shyr ZA, Huang Y, Reissaus CA, Meyer D, Piston DW, Hyrc K, Remedi MS, Nichols CG. Beta-cell excitability and excitability-driven diabetes in adult Zebrafish islets. Physiological Reports 2019 Jun;7(11):e14101. 10.14814/phy2.14101. Pubmed

Lorincz R, Emfinger CH, Walcher A, Giolai M, Krautgasser C, Remedi MS, Nichols CG, Meyer D. In vivo monitoring of intracellular Ca2+ dynamics in the pancreatic β-cells of zebrafish Embryos.In Islets 2018;10(6):221-238. (DOI) 2018.1540234. Epub 2018 Dec 6. Pubmed

Facchinello, N; Tarifeño-Saldivia, E; Grisan, E; Schiavone, M; Peron, M; Mongera, A; Ek, O; Schmitner, N; Meyer, D; Peers, B; Tiso, N; Argenton, F; (2017) Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and Regeneration. In Scientific Reports 2017; 7: 9605. Published online 2017 Aug 29. (DOI) Pubmed

Kimmel, R.A.; Meyer, D. (2016) Zebrafish Pancreas as a Model for Development and Disease. Methods in Cell Biology, available online 17 March 2016. doi:10.1016/bs.mcb.2016.02.009 .  Pubmed

Kimmel, R.A., Dobler, S., Schmitner, N., Walsen, T., Freudenblum, J., and Meyer, D. (2015). Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment. Sci. Rep. 5, 14241 Pubmed (doi: 10.1038/srep14241 ) (https://www.nature.com/articles/srep14241)

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