Activated pancreatic stellate cells can impair pancreatic islet function in mice

  • Guangxiang Zang Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
  • Monica Sandberg Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
  • Per-Ola Carlsson Department of Medical Cell Biology, Uppsala University, Uppsala, and Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  • Nils Welsh Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
  • Leif Jansson Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
  • Andreea Barbu Department of Medical Cell Biology, Uppsala University, Uppsala, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Keywords: Beta-cell replication, insulin release, pancreatic islets, stellate cells

Abstract

Background. Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.

Methods. Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.

Results. PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets cocultured with PSCs for 24–48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

Conclusion. Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.

Downloads

Download data is not yet available.
Published
2015-04-08
How to Cite
Zang, G., Sandberg, M., Carlsson, P.-O., Welsh, N., Jansson, L., & Barbu, A. (2015). Activated pancreatic stellate cells can impair pancreatic islet function in mice. Upsala Journal of Medical Sciences, 120(3). https://doi.org/10.3109/03009734.2015.1032453
Section
Original Articles

Most read articles by the same author(s)