ESPE Yearbook of Paediatric Endocrinology

Stem Cell Res. 2021 Jul;54:102433. doi: 10.1016/j.scr.2021.102433. PMID: 34171785.

Brief Summary: This study generated induced pluripotent stem cells (iPSCs) from a patient with permanent neonatal diabetes mellitus (PNDM) due to Fanconi-Bickel syndrome. This iPSC line provides a novel human cell model to understand the pathophysiology of FBS and diabetes mellitus and for the potential of developing and testing new pharmacological treatments.

Fanconi-Bickel syndrome (FBS) is a rare disorder caused by homozygous mutations in the SLC2A2 gene. This gene encodes for the GLUT2 glucose transporter which is expressed in the pancreatic beta-cells, liver, central nervous system and the kidney. Some patients with FBS may present with permanent neonatal diabetes mellites (PNDM). GLUT2 seems to have an important role in beta-cell physiology but the underlying mechanisms involved are not known (1). Thus, having a cell line which has a mutated GLUT2 would be very useful to study the mechanisms of GLUT2 and pancreatic beta-cell physiology. Using the patient’s peripheral mononuclear cells (PBMCs), the authors generated iPSCs from a patient with a homozygous nonsense mutation in the SLC2A2 gene and PNDM.

The PBMCs were reprogramed into a pluripotent state using the non-integrating Sendai virus vector expressing OCT4, SOX2, c-MYC, and KLF4. The mutation (c.901C T) in the SLC2A2 gene was confirmed in the generated iPSC line using sanger sequencing. The generated cell line displayed an identical morphology of the human embryonic stem cell colonies and expressed the key pluripotency markers, including OCT4, SSEA4, SOX2, TRA-1–60, NANOG, TRA81, c-MYC, KLF4, REX1 and TERT as examined by immunocytochemistry, RT-PCR, and flow cytometry analyses.

This iPSC line provides a novel human cell model to understand the pathophysiology of FBS and diabetes mellitus associated with SLC2A2 defects and for the potential of testing new pharmacological treatments.

Reference: 1. Sharari S, Abou-Alloul M, Hussain K, Ahmad Khan F. Fanconi-Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia. Int J Mol Sci. 2020;21(17):E6286.