Manara - Qatar Research Repository
10.1186_s12967-022-03327-5.pdf (857.89 kB)

β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells?

Download (857.89 kB)
journal contribution
submitted on 2024-04-16, 05:50 and posted on 2024-04-16, 05:51 authored by Abdoulaye Diane, Noora Ali Al-Shukri, Razik Bin Abdul Mu-u-min, Heba H. Al-Siddiqi

Diabetes mellitus (DM), currently affecting 463 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from the loss or dysfunction of pancreatic β-cells with the former preponderating in type 1 diabetes (T1DM) and the latter in type 2 diabetes (T2DM). Because impaired insulin secretion due to dysfunction or loss of pancreatic β-cells underlies different types of diabetes, research has focused its effort towards the generation of pancreatic β-cells from human pluripotent stem cell (hPSC) as a potential source of cells to compensate for insulin deficiency. However, many protocols developed to differentiate hPSCs into insulin-expressing β-cells in vitro have generated hPSC-derived β-cells with either immature phenotype such as impaired glucose-stimulated insulin secretion (GSIS) or a weaker response to GSIS than cadaveric islets. In pancreatic β-cells, mitochondria play a central role in coupling glucose metabolism to insulin exocytosis, thereby ensuring refined control of GSIS. Defects in β-cell mitochondrial metabolism and function impair this metabolic coupling. In the present review, we highlight the role of mitochondria in metabolism secretion coupling in the β-cells and summarize the evidence accumulated for the implication of mitochondria in β-cell dysfunction in DM and consequently, how targeting mitochondria function might be a new and interesting strategy to further perfect the differentiation protocol for generation of mature and functional hPSC-derived β-cells with GSIS profile similar to human cadaveric islets for drug screening or potentially for cell therapy.

Other Information

Published in: Journal of Translational Medicine
See article on publisher's website:



  • English


Springer Nature

Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Diabetes Research Center - QBRI

Usage metrics

    Qatar Biomedical Research Institute - HBKU



    Ref. manager