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Michele Solimena Group

Cell Biology of Pancreatic Beta Cells and Pathogenesis of Diabetes

Portrait Michele Solimena

Our laboratory is interested in the cell biology of pancreatic beta cells, which produce and secrete insulin. A deficient output of insulin secretion relative to metabolic demands is the ultimate cause of all forms of diabetes mellitus. Beta cells store the insulin hormone within organelles termed secretory granules, which undergo fusion with the plasma membrane and release insulin in response to high levels of circulating glucose. Prolonged glucose stimulation depletes beta cells of insulin secretory granules, which must be quickly replenished.

The main question we are addressing is how beta cells regulate the turnover of insulin secretory granules, including their biogenesis, exocytosis and destruction. A mechanistic description of these processes may provide insight into the pathogenesis of type 1 and type 2 diabetes and contribute to the development of novel approaches for its treatment. These studies may also have general implications in the field of neuropeptide and peptide-hormone secretion from neurons and other endocrine cells.

Specifically, we are addressing the following key questions:

  • How is a beta cell counting its own insulin secretory granules?
  • Which are the molecular signatures associated with granule aging?
  • What accounts for the reduced mobility and propensity to undergo exocytosis of older versus younger insulin secretory granules?
  • Which posttranscriptional mechanisms allow glucose and other stimuli to prompt the rapid biogenesis of insulin secretory granules?
  • Which retrograde signaling pathways couple the exocytosis of insulin secretory granules with regulation of beta cell gene expression and replication?

Moreover, we are pursuing:

  • siRNA and small compound high-throughput screenings for the identification of genes and drugs of potential interest for the therapy of diabetes
  • the identification of genes differentially expressed in pancreatic beta cells of euglycemic and type 2 diabetic subjects as well as of individuals with impaired glucose tolerance secondary to insulin resistance
  • the elucidation how enteroviruses potentially implicated in the pathogenesis of type 1a diabetes may trigger autoimmunity against insulin granule proteins
Michele Solimena Research: Figure
Figure: Correlation light-electron microscopy (CLEM) imaging of the same pancreatic beta cells from the Sofia Mouse (Ivanova et al, 2013) by sequential super resolution (A) and transmission electron (B) microscopy. (A) The fluorescent signals detected by super resolution microscopy (SRM) correspond to nucleus (blue), insulin secretory granules less than 2 hour-old (red), all insulin secretory granules (green). (B) Magnified view of the area indicated in A by transmission electron microscopy (TEM) followed by overlay of the images obtained by SRM and TEM: nucleus (N) secretory granules (SG) (C) Nucleocytoplasmic translocation of the mRNA binding protein PTBP1 (in yellow) in beta cells upon stimulation with IBMX. Nuclei of islet cells are labeled in blue. Credits: (A) & (B): Andreas Müller, Anna Ivanova, Michele Solimena; (C): Klaus Knoch, Michele Solimena

Future Projects and Goals

To address these questions we employ a large array of quantitative imaging, molecular, and biochemical approaches using insulinoma cultured cells, isolated pancreatic islets and genetically modified mice as main model systems. We actively collaborate with structural biologists, biophysicists, bioinformaticians and mathematicians to deepen our understanding at the level of single molecules and to elaborate in-silico predictive models of these processes. Through the collaboration with clinicians at our University we extend our investigations to human islets from non-diabetic as well as diabetic subjects.

Methodological and Technical Expertise

  • RNA and protein biochemistry
  • TIRF microscopy
  • CLEM (Correlation light electron microscopy)
  • Transgenic mice
  • Laser capture microdissection

Currently Recruiting

Michele Solimena is recruiting in the PhD Summer Selection 2024 (call is closed)

Open Project
  • Cell biology of viruses in pancreatic beta cells and type 1 diabetes
    Preferred Course of Study/Expertise of Candidate: Molecular cell biology, membrane trafficking, virology, antigen presentation

    This project will be conducted through collaboration between TUD, the University of Zurich, and ETH Zurich. It is part of the International Research Training Group Metabolic and Endocrine Drivers of Infection Susceptibility (IRTG3019). Within this collaboration, students will have the opportunity to obtain a joint certificate from TUD and the universities in Zurich.


since July 2009
Speaker Paul Langerhans Institute Dresden, German Center for Diabetes Research

since July 2009
Professor of Molecular Diabetology, Medical School TU Dresden

since 2007
Fellow of the Max Planck Society

since 2003
Professor of Experimental Diabetology, Medical School, TU Dresden

Group Leader at Max Planck Institute of Molecular Cell Biology and Genetics, Dresden

Associate Professor, Dept. of Internal Medicine and Cell Biology, Yale Univ. School of Medicine

Assistant Professor, Dept. of Internal Medicine, Yale Univ. School of Medicine

Postdoctoral fellow at Dept. of Cell Biology, Yale Univ. School of Medicine, New Haven, CT, USA

Postdoctoral work at Dept. of Pharmacology and Toxicology, University of Milano

Ph.D., University of Milano School of Medicine, Italy

M.D, University of Milano School of Medicine, Italy

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Selected Publications

Neukam M, Sala P, Brunner AD, Ganß K, Palladini A, Grzybek M, Topcheva O, Vasiljević J, Broichhagen J, Johnsson K, Kurth T, Mann M, Coskun Ü, Solimena M
Purification of time-resolved insulin granules reveals proteomic and lipidomic changes during granule aging
Cell Rep 43(3):113836. doi: 10.1016/j.celrep.2024.113836 (2024)

Gloyn AL, Ibberson M, Marchetti P, Powers AC, Rorsman P, Sander M, Solimena M
Every islet matters: improving the impact of human islet research.
Nat Metab. 4:970–977 (2022)

Xu CS, Pang S, Shtengel G, Müller A, Ritter AT, Hoffman HK, Takemura SY, Lu Z, Pasolli HA, Iyer N, Chung J, Bennett D, Weigel AV, Freeman M, van Engelenburg SB, Walther TC, Farese RV Jr, Lippincott-Schwartz J, Mellman I, Solimena M, Hess HF
An open-access volume electron microscopy atlas of whole cells and tissues
Nature. 599:147–151 (2021)

Wigger L, Barovic M, Brunner AD, Marzetta F, Schöniger E, Mehl F, Kipke N, Friedland D, Burdet F, Kessler C, Lesche M, Thorens B, Bonifacio E, Legido-Quigley C, Barbier Saint Hilaire P, Delerive P, Dahl A, Klose C, Gerl MJ, Simons K, Aust D, Weitz J, Distler M, Schulte AM, Mann M, Ibberson M, Solimena M
Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes
Nat Metab. 3:1017–1031 (2021)

Müller A, Schmidt D, Xu CS, Pang S, D’Costa JV, Kretschmar S, Münster C, Kurth T, Jug F, Weigert M, Hess HF, Solimena M
3D FIB-SEM reconstruction of microtubule-organelle interaction in whole primary mouse β cells
J Cell Biol. 220:e202010039 (2021)


Molecular Diabetology & DZD-Paul Langerhans Institute Dresden
TU Dresden
c/o BioZ
Tatzberg 47/49
D-01307 Dresden