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Int. J. Mol. Sci. 2018, 19(4), 943; https://doi.org/10.3390/ijms19040943

α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
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Received: 11 February 2018 / Revised: 12 March 2018 / Accepted: 15 March 2018 / Published: 22 March 2018
(This article belongs to the Section Biochemistry)
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Abstract

A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133+ and CD133 cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133+ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet. View Full-Text
Keywords: pancreatic progenitor-like cells; α-ketoglutarate; proliferation pancreatic progenitor-like cells; α-ketoglutarate; proliferation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Song, J.; Ma, D.; Xing, Y.; Tang, S.; Alahdal, M.; Guo, J.; Pan, Y.; Zhang, Y.; Shen, Y.; Wu, Q.; Lu, Z.; Jin, L. α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation. Int. J. Mol. Sci. 2018, 19, 943.

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