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Stephan Speier Group

Islet of Langerhans Physiology in the Pathogenesis and Therapy of Diabetes

Portrait Stephan Speier



Diabetes is a growing epidemic with major impact on life style, health and life expectancy of the affected patients. Diabetes develops when systemic insulin concentrations are insufficient to control blood glucose homeostasis. This shortage in insulin is either caused by a functional deterioration of insulin secreting pancreatic beta cells or by a loss of their mass (reduced cell number). Recent research by our and other groups has shown that in different phases of type 1 and type 2 diabetes pathogenesis the contribution of changes in beta cell mass and/or function varies (→ Figure 1).

Based on these findings we believe that successful treatment of diabetes depends on targeting beta cell dysfunction and mass loss in specific phases of pathogenesis.

Thus, our group investigates the role of beta cell mass and function at distinct stages of diabetes pathogenesis and aims to discover novel therapeutic targets for beta cell protection and recovery in type 1 and type 2 diabetes. A central aspect of our research is the translation of our findings into the human setting by utilizing novel platforms to study human pancreatic tissue and islets. In addition, we utilize our unique platforms to optimize alternative cell sources for the successful generation of cell replacement therapies for diabetes.


The unique approach of our lab is the study of islet cell physiology within an intact tissue environment or the systemic setting. For that purpose we have established novel in situ and in vivo techniques to complement standard methods of islet research. Thereby, we aim to account for the numerous local and systemic signals which affect the physiology and pathogenesis of islets within the organ tissue and inside the living organism.

For example, the pancreas tissue slice platform allows us to study the human pancreas from organ and tissue donors to assess for the first time human islet cell pathophysiology within an intact organ tissue environment (→ Figure 2).

In addition, our in vivo imaging platform facilitates the noninvasive longitudinal observation of islet physiology in a systemic setting for prolonged time periods. This unique setup enables for the first time to study islet cells during changing metabolic conditions and disease pathogenesis (→ Figure 3).

Stephan Speier Research: Figure 1
Figure 1. Models of the contribution of beta cell mass and function to pathogenesis of type 1 diabetes (A) and type 2 diabetes (B). Black line: beta cell mass; Blue line: beta cell function. The color-coded background indicates the intensity of beta cell workload and stress caused by insulin resistance, metabolic demand, hyperglycemia and additional cytotoxic factors. (Chen et al, Mol Metab, 2017)
Stephan Speier Research: Figure 2
Figure 2. Left: Maximum intensity projection of a human pancreas tissue slice stained with antibodies against insulin (green), glucagon (magenta), and somatostatin (grey) counterstained with DAPI (blue). Scale bar, 500 mm. Right: Insulin secretory pattern of pancreas tissue slices from non-diabetic (ND) (green), impaired glucose tolerant (IGT) (blue), and type 2 diabetic (T2D) (orange) donors during perifusion. (Cohrs et al, Cell Rep, 2020)
Stephan Speier Research: Figure 3
Figure 3: Longitudinal in vivo observation of autoimmune beta cell destruction during type 1 diabetes progression. Green: beta cells; Magenta: blood vessels; Grey: cell lightscatter. (Chmelova et al, Diabetes, 2015)

Future Projects and Goals

  • Assessing the mechanism of beta cell dysfunction in diabetes pathogenesis
  • Facilitating the development of cell therapies for diabetes
  • Translation of research findings to human

Methodological and Technical Expertise

  • in vivo, in situ and in vitro two-photon and confocal laser scanning microscopy
  • patch-clamp technique
  • assessment of cell and systemic physiology in animal models
  • novel platforms to study human islets of Langerhans and pancreas tissue

Currently Recruiting

Stephan Speier is recruiting in the PhD Summer Selection 2024 (call is closed)

Open Project
  • In vivo maturation and resilience of stem cell derived islets after transplantation
    Preferred Course of Study/Expertise of Candidate: Cell Biology, Physiology, Medicine


since 2022
Professor of Physiology
Director, Institute of Physiology, Faculty of Medicine, TU Dresden
Research Group Leader, DZD-Paul Langerhans Institute Dresden (PLID)

Professor for Pancreatic Islet Physiology, Faculty of Medicine, TU Dresden
Islet Cell Physiology Group, DZD-Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Hospital and Faculty of Medicine, TU Dresden

Group Leader, Center for Regenerative Therapies Dresden (CRTD) and Paul-Langerhans Institute Dresden (PLID)

Emmy Noether Fellow

Postdoctoral Research Fellow, The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institute, Stockholm, Sweden

Postdoctoral Research Fellow, European Neuroscience Institute Göttingen / Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

PhD Thesis, European Neuroscience Institute Göttingen / Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

Diploma degree in Human Biology, Philipps-University Marburg, Institute for Normal and Pathological Physiology, Marburg, Germany

Selected Publications

Cohrs CM, Panzer JK, Drotar DM, Enos SJ, Kipke N, Chen C, Bozsak R, Schöniger E, Ehehalt F, Distler M, Brennand A, Bornstein SR, Weitz J, Solimena M, Speier S
Dysfunction of Persisting beta Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis.
Cell Rep; 31, 107469 (2020)

Panzer JK, Hiller H, Cohrs CM, Almaça J, Enos SJ, Beery M, Cechin S, Drotar DM, Weitz JR, Santini J, Huber MK, Muhammad Fahd Qadir M, Pastori RL, Domínguez-Bendala J, Phelps EA, Atkinson MA, Pugliese A, Caicedo A, Kusmartseva I, Speier S
Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis.
JCI Insight; 5 (2020)

Chen C, Chmelova H, Cohrs CM, Chouinard JA, Jahn SR, Stertmann J, Uphues I, Speier S.
Alterations in beta-Cell Calcium Dynamics and Efficacy Outweigh Islet Mass Adaptation in Compensation of Insulin Resistance and Prediabetes Onset.
Diabetes; 65, 2676–2685 (2016)

Marciniak A, Cohrs CM, Tsata V, Chouinard JA, Selck C, Stertmann J, Reichelt S, Rose T, Ehehalt F, Weitz J, Solimena M, Slak Rupnik M, Speier S
Using pancreas tissue slices for in situ studies of islet of Langerhans and acinar cell biology.
Nature Protocols; 9, 2809–2822 (2014)

peier S, Nyqvist D, Cabrera O, Yu J, Molano RD, Pileggi A, Moede T, Köhler M, Wilbertz J, Leibiger B, Ricordi C, Leibiger IB, Caicedo A, Berggren PO
Noninvasive in vivo imaging of pancreatic islet cell biology.
Nature Medicine; 14, 574–578 (2008)


Institute of Physiology
Faculty of Medicine
Fetscherstraße 74
01307 Dresden