Human islet microtissues as an in vitro and an in vivo model system for diabetes

Joan Mir-Coll, Tilo Moede, Meike Paschen, Aparna Neelakandhan, Ismael Valladolid-Acebes, Barbara Leibiger, Adelinn Biernath, Carina Ämmälä, Ingo B. Leibiger, Burcak Yesildag, Per Olof Berggren

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Loss of pancreatic β-cell function is a critical event in the pathophysiology of type 2 diabetes. However, studies of its underlying mechanisms as well as the discovery of novel targets and therapies have been hindered due to limitations in available experimental models. In this study we exploited the stable viability and function of standardized human islet microtissues to develop a disease-relevant, scalable, and reproducible model of β-cell dysfunction by exposing them to long-term glucotoxicity and glucolipotoxicity. Moreover, by establishing a method for highly-efficient and homogeneous viral transduction, we were able to monitor the loss of functional β-cell mass in vivo by transplanting reporter human islet microtissues into the anterior chamber of the eye of immune-deficient mice exposed to a diabetogenic diet for 12 weeks. This newly developed in vitro model as well as the described in vivo methodology represent a new set of tools that will facilitate the study of β-cell failure in type 2 diabetes and would accelerate the discovery of novel therapeutic agents.

Original languageEnglish
Article number1813
Pages (from-to)1-26
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume22
Issue number4
DOIs
Publication statusPublished - 11 Feb 2021

Keywords

  • Diabetes
  • Diet-induced obesity
  • Glucolipotoxicity
  • Glucotoxicity
  • Insulin resistance
  • Pancreatic islets
  • Transplantation
  • Viral transduction
  • β-cell dysfunction
  • Humans
  • Insulin-Secreting Cells/metabolism
  • Male
  • Mice, Knockout
  • Diabetes Mellitus, Experimental/metabolism
  • Animals
  • Heterografts
  • Islets of Langerhans Transplantation
  • Diabetes Mellitus, Type 2/metabolism
  • Mice, Inbred NOD

Fingerprint

Dive into the research topics of 'Human islet microtissues as an in vitro and an in vivo model system for diabetes'. Together they form a unique fingerprint.

Cite this