Please use this identifier to cite or link to this item:
Title: Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant ? cells
Authors: Low, Blaise Su Jun
Lim, Chang Siang 
Ding, Shirley Suet Lee
Tan, Yaw Sing
Ng, Natasha Hui Jin
Krishnan, Vidhya Gomathi
Ang, Su Fen
Neo, Claire Wen Ying
Verma, Chandra S. 
Hoon, Shawn
Lim, Su Chi 
Tai, E. Shyong 
Teo, Adrian Kee Keong 
Issue Date: 25-May-2021
Publisher: Nature Research
Citation: Low, Blaise Su Jun, Lim, Chang Siang, Ding, Shirley Suet Lee, Tan, Yaw Sing, Ng, Natasha Hui Jin, Krishnan, Vidhya Gomathi, Ang, Su Fen, Neo, Claire Wen Ying, Verma, Chandra S., Hoon, Shawn, Lim, Su Chi, Tai, E. Shyong, Teo, Adrian Kee Keong (2021-05-25). Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant ? cells. Nature Communications 12 (1) : 3133. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Heterozygous HNF1A gene mutations can cause maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. However, specific mechanisms of MODY3 in humans remain unclear due to lack of access to diseased human pancreatic cells. Here, we utilize MODY3 patient-derived human induced pluripotent stem cells (hiPSCs) to study the effect(s) of a causal HNF1A+/H126D mutation on pancreatic function. Molecular dynamics simulations predict that the H126D mutation could compromise DNA binding and gene target transcription. Genome-wide RNA-Seq and ChIP-Seq analyses on MODY3 hiPSC-derived endocrine progenitors reveal numerous HNF1A gene targets affected by the mutation. We find decreased glucose transporter GLUT2 expression, which is associated with reduced glucose uptake and ATP production in the MODY3 hiPSC-derived ?-like cells. Overall, our findings reveal the importance of HNF1A in regulating GLUT2 and several genes involved in insulin secretion that can account for the insulin secretory defect clinically observed in MODY3 patients. © 2021, The Author(s).
Source Title: Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-021-22843-4
Rights: Attribution 4.0 International
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_s41467-021-22843-4.pdf7.44 MBAdobe PDF



Google ScholarTM



This item is licensed under a Creative Commons License Creative Commons