Islet Cell Physiology
Previous and Current Research
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. Recent research of our lab and other groups has demonstrated that simultaneous deteriorations of both, number and function of insulin secreting beta cells are the cause of this shortage in insulin. Thereby, the different phases of diabetes pathogenesis are characterized by distinct alterations of beta cell mass and/or function. Based on these findings we believe that parallel targeting of beta cell function and mass is necessary to successfully treat diabetes. Thus, our group aims to discover novel therapeutic targets for type 1, type 2 and gestational diabetes by investigating the role of beta cell mass and function at distinct stages of diabetes pathogenesis and therapy.
Targeting beta cell function
Beta cell function exhibits enormous plasticity in response to various physiological and pathophysiological situations. Under normal conditions functional compensation of insulin secretion significantly contributes to preventing the development of type 2 diabetes and gestational diabetes. However, in diabetes pathogenesis beta cell dysfunction hinders functional compensation resulting in hyperglycemia. Thus, our projects addressing beta cell function aim to reveal the underlying mechanisms of functional compensation and beta cell dysfunction to protect and recover beta cell function in diabetes therapy.
Targeting beta cell mass
Also the number of beta cells can increase during obesity and pregnancy in an attempt to balance the greater insulin demand under these conditions. However, the regenerative mechanisms underlying this enlargement of beta cell mass as well as the reasons for its failure during the development of type 2 diabetes and gestational diabetes are unclear. We aim to understand the bases of beta cell regeneration to enable their induction in the prevention of type 2 diabetes and gestational diabetes. In addition, we use our expertise to facilitate the development of functionally mature beta cells from embryonic stem cells for cell replacement therapies of type 1 diabetes.
The unique approach of our lab in tackling these tasks is the study of islet of Langerhans mass and function under most physiological conditions. Thereby, we aim to account for the numerous local and systemic signals which regulate the complex physiology of islet pathology and regeneration inside the living organism. For that purpose we have established novel in situ and in vivo technical platforms to complement standard methods of islet research.
A key aspect of our work is the translation of our research to the human situation. Over the last years we have built up national and international collaborations to obtain acute human tissue, giving us the unique opportunity to employ our techniques for the investigation of human diabetes therapies.
Future Projects and Goals
- Assessing the mechanism of beta cell dysfunction in diabetes pathogenesis
- Evaluating the mechanism of endogenous islet cell regeneration
- Facilitating the development of mature stem cell derived beta cells
- 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
- human and mouse islets of Langerhans and tissue slices
Chen C, Chmelova H, Cohrs CM, Chouinard JA, Jahn SR, Stertmann J, Uphues I, Speier S
Alterations in β-cell calcium dynamics and efficacy outweigh islet mass adaptation in compensation of insulin resistance and prediabetes onset.
Diabetes; 65:2676–85 (2016)
Chmelova H, Cohrs CM, Chouinard JA, Petzold C, Kuhn M, Chen C, Roeder I, Kretschmer K, Speier S
Distinct roles of beta cell mass and function during type 1 diabetes onset and remission.
Diabetes; 64:2148–2160. (2015)
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.
Nat Protoc;9:2809–2822 (2014)
Marciniak A, Selck C, Friedrich B, Speier S
Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.
PLoS One;8:e78706. (2013)
Speier S, Nyqvist D, Cabrera O, Yu J, Molano RD, Pileggi A, Moede T, Kohler M, Wilbertz J, Leibiger B, Ricordi C, Leibiger IB, Caicedo A, Berggren PO
Noninvasive in vivo imaging of pancreatic islet cell biology.
Nat Med;14:574–578 (2008)