Detail

Keywords

Endocrinology; Insulin-Secreting Cells; Neuroendocrinology; Pancreas; Physiology

Research group(s)

• Cell and tissue networks
  Head: Marjan Slak Rupnik
  Research Area: Collective activity presents a basic mode of operation in complex cell and tissue network activity and can be assessed using various advanced computational tools (complex network, spin glass model, phase flipping model, random matrix theory).
  Members:
  Srdjan Sarikas
  Sandra Postic
  Johannes Pfabe
  Marjan Slak Rupnik
  Anita Krnjic

Research interests

Our laboratory pioneered a routine use of pancreas tissue slices to study the function of insulin-secreting beta cells in adult (Speier and Rupnik, 2003; Rupnik 2009), perinatal mice (Meneghel-Rozzo et al., 2004; Rozzo et al., 2009), normal and diabetic rats (Rose at al., 2007). We contributed to the knowledge-base on the function of KATP channels (Speier et al., 2005; Tsiaze et al, 2012), NMDA receptors (Marquard et al., 2015), and SNAP25b (Daraio et al., 2017) within an intact pancreatic tissue.

Recently, we developed a high-throughput analysis platform that enabled us to study IP3 and ryanodine receptors and reveal that under physiological conditions, these receptors are necessary and sufficient to support the activation and long-term activity of beta cells (Sluga et al, 2022, Postic et al., 2023a, Sluga et al, 2023, Postic et al., 2023b).

The complex structure of the pancreatic islet network enabled us to describe emergent properties of the beta cell function in intact tissues (Stozer et al, 2013; Stozer et al, 2013, Dolenšek et al., 2013, Markovic et al., 2015, Korosak and Slak Rupnik, 2018). Such a complex behavior is a basis of biological computation serving the metabolic economy in an organism (Korosak et al., 2023).

Techniques, methods & infrastructure

• confocal and multiphoton microscopy
• computational cell collective analyses
• patch-clamp & CCD imaging in fresh pancreas slices

Grants

• R01DK127236 Control of beta cell function and survival by RYR2-mediated calcium signals (oo-ordinated by Carmella Evans-Molina, UI) (2021)
  Source of Funding: National Institutes of Health (NIH), Cellular Aspects of Diabetes and Obesity Study Section
  Principal Investigator
• Beta-cells in diet-induced diabetes and remission (2019)
  Source of Funding: FWF (Austrian Science Fund), Joint Project; FWF-ARRS
  Coordinator of the collaborative project
• Cell and Tissue Networks (2019)
  Source of Funding: Slovenian Research Agency (ARRS), Research Programs
  Principal Investigator
• Linking Islet Cell Function and Identity from in vitro to in situ (2018)
  Source of Funding: National Institutes of Health (NIH), NIDKK - Human Islet Research Network
  Principal Investigator
• pH-sensitive TALK1 channels in islet-ductal interactions (2017)
  Source of Funding: FWF (Austrian Science Fund), International Joint Project; FWF-MOST (Taiwan)
  Coordinator of the collaborative project
• The role of TRPM3 and TRPM5 in the regulation of network activity in pancreatic islets (2017)
  Source of Funding: Slovenian Research Agency (ARRS), International Joint Project, FWO-ARRS
  Principal Investigator

Selected publications

1. Rizk, A.A. et al. (2023) ‘Pancreatic regional blood flow links the endocrine and exocrine diseases’, Journal of Clinical Investigation, 133(15). Available at: http://dx.doi.org/10.1172/jci166185.
2. Postić, S. et al. (2023) ‘Tracking Ca2+ Dynamics in NOD Mouse Islets During Spontaneous Diabetes Development’, Diabetes, 72(9), pp. 1251–1261. Available at: http://dx.doi.org/10.2337/db22-0952.
3. Korošak, D. et al. (2023) ‘Collective biological computation in metabolic economy’, 4open, 6, p. 3. Available at: http://dx.doi.org/10.1051/fopen/2023002.
4. Postić, S. et al. (2023) ‘High-resolution analysis of the cytosolic Ca2+ events in β cell collectives in situ’, American Journal of Physiology-Endocrinology and Metabolism, 324(1), pp. E42–E55. Available at: http://dx.doi.org/10.1152/ajpendo.00165.2022.
5. Sluga, N. et al. (2022) ‘Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels’, Frontiers in Endocrinology, 13. Available at: http://dx.doi.org/10.3389/fendo.2022.1013697.