Hong Yeonhee, Park Eun-Young, Kim Donghee, Lee Hakmo, Jung Hye Seung, Jun Hee-Sook
College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
Ann Transl Med. 2020 Apr;8(8):561. doi: 10.21037/atm.2020.03.103.
Islet transplantation might be a logical strategy to restore insulin secretion for the treatment of diabetes, however, the scarcity of donors poses an obstacle for such a treatment. As an alternative islet source, differentiation of stem cells into insulin-producing cells (IPCs) has been tried. Many protocols have been developed to improve the efficiency of differentiation of stem cells into IPCs. In this study, we investigated whether glucosamine supplementation during differentiation of human adipose-derived stem cells (hADSCs) into IPCs can improve the insulin secretory function.
Glucosamine was added to the original differentiation medium at different stages of differentiation of hADSCs into IPCs for 12 days and insulin secretion was analyzed.
Addition of glucosamine alone to the growth medium of hADSCs did not affect the differentiation of hADSCs to IPCs. Supplementation of the differentiation medium with glucosamine at a later stage (protocol G3) proved to have the greatest effect on IPC differentiation. Basal and glucose-stimulated insulin secretion (GSIS) was significantly increased and the expression of insulin and C-peptide was increased in differentiated IPCs as compared with that in differentiated IPCs using the conventional protocol (protocol C). In addition, the expression of beta-cell specific transcription factors such as pancreatic and duodenal homeobox1 (PDX1) and neurogenin 3 (NGN3) was also increased. Furthermore, the expression of genes related to insulin secretion, including synaptotagmin 4 (Syt4), glucokinase (Gck) and glucose transporter 2 (Glut2), was also increased.
We conclude that glucosamine supplementation potentiates the differentiation of hADSCs into IPCs.
胰岛移植可能是恢复胰岛素分泌以治疗糖尿病的合理策略，然而，供体的稀缺对这种治疗构成了障碍。作为替代的胰岛来源，已尝试将干细胞分化为胰岛素产生细胞（IPCs）。已经开发了许多方案来提高干细胞向IPCs分化的效率。在本研究中，我们调查了在人脂肪来源干细胞（hADSCs）向IPCs分化过程中补充氨基葡萄糖是否能改善胰岛素分泌功能。
在hADSCs向IPCs分化的不同阶段，将氨基葡萄糖添加到原始分化培养基中12天，并分析胰岛素分泌情况。
单独向hADSCs的生长培养基中添加氨基葡萄糖不影响hADSCs向IPCs的分化。在分化后期（方案G3）向分化培养基中补充氨基葡萄糖对IPCs分化的影响最大。与使用传统方案（方案C）分化的IPCs相比，分化后的IPCs基础胰岛素分泌和葡萄糖刺激的胰岛素分泌（GSIS）显著增加，胰岛素和C肽的表达增加。此外，胰腺和十二指肠同源盒1（PDX1）和神经生成素3（NGN3）等β细胞特异性转录因子的表达也增加。此外，与胰岛素分泌相关的基因，包括突触结合蛋白4（Syt4）、葡萄糖激酶（Gck）和葡萄糖转运蛋白2（Glut2）的表达也增加。
我们得出结论，补充氨基葡萄糖可增强hADSCs向IPCs的分化。
