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A-Ryeong Gwon  (Gwon AR) 1 Article
Basic Research
Notch1 Has an Important Role in β-Cell Mass Determination and Development of Diabetes
Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Jin-Young Youn, Heekyoung Park, Kwang-Won Kim, Byung-Joon Kim
Diabetes Metab J. 2021;45(1):86-96.   Published online February 26, 2020
DOI: https://doi.org/10.4093/dmj.2019.0160
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  • 7 Web of Science
  • 6 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Notch signaling pathway plays an important role in regulating pancreatic endocrine and exocrine cell fate during pancreas development. Notch signaling is also expressed in adult pancreas. There are few studies on the effect of Notch on adult pancreas. Here, we investigated the role of Notch in islet mass and glucose homeostasis in adult pancreas using Notch1 antisense transgenic (NAS).

Methods

Western blot analysis was performed for the liver of 8-week-old male NAS mice. We also conducted an intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test in 8-week-old male NAS mice and male C57BL/6 mice (control). Morphologic observation of pancreatic islet and β-cell was conducted in two groups. Insulin secretion capacity in islets was measured by glucose-stimulated insulin secretion (GSIS) and perifusion.

Results

NAS mice showed higher glucose levels and lower insulin secretion in IPGTT than the control mice. There was no significant difference in insulin resistance. Total islet and β-cell masses were decreased in NAS mice. The number of large islets (≥250 µm) decreased while that of small islets (<250 µm) increased. Reduced insulin secretion was observed in GSIS and perifusion. Neurogenin3, neurogenic differentiation, and MAF bZIP transcription factor A levels increased in NAS mice.

Conclusion

Our study provides that Notch1 inhibition decreased insulin secretion and decreased islet and β-cell masses. It is thought that Notch1 inhibition suppresses islet proliferation and induces differentiation of small islets. In conclusion, Notch signaling pathway may play an important role in β-cell mass determination and diabetes.

Citations

Citations to this article as recorded by  
  • N6-methylation of RNA-bound adenosine regulator HNRNPC promotes vascular endothelial dysfunction in type 2 diabetes mellitus by activating the PSEN1-mediated Notch pathway
    Ying Cai, Tao Chen, Mingzhu Wang, Lihua Deng, Cui Li, Siqian Fu, Kangling Xie
    Diabetes Research and Clinical Practice.2023; 197: 110261.     CrossRef
  • Single‐cell RNA sequencing: Inhibited Notch2 signalling underlying the increased lens fibre cells differentiation in high myopia
    Yunqian Yao, Ling Wei, Zhenhua Chen, Hao Li, Jiao Qi, Qingfeng Wu, Xingtao Zhou, Yi Lu, Xiangjia Zhu
    Cell Proliferation.2023;[Epub]     CrossRef
  • Micro ribonucleic acid‐363 regulates the phosphatidylinositol 3‐kinase/threonine protein kinase axis by targeting NOTCH1 and forkhead box C2, leading to hepatic glucose and lipids metabolism disorder in type 2 diabetes mellitus
    Yu‐Huan Peng, Ping Wang, Xiao‐Qun He, Ming‐Zhao Hong, Feng Liu
    Journal of Diabetes Investigation.2022; 13(2): 236.     CrossRef
  • Soluble T-cadherin promotes pancreatic β-cell proliferation by upregulating Notch signaling
    Tomonori Okita, Shunbun Kita, Shiro Fukuda, Keita Fukuoka, Emi Kawada-Horitani, Masahito Iioka, Yuto Nakamura, Yuya Fujishima, Hitoshi Nishizawa, Dan Kawamori, Taka-aki Matsuoka, Maeda Norikazu, Iichiro Shimomura
    iScience.2022; 25(11): 105404.     CrossRef
  • Comparison of islet isolation result and clinical applicability according to GMP‐grade collagenase enzyme blend in adult porcine islet isolation and culture
    Kyungmin Kwak, Jae‐kyung Park, Joohyun Shim, Nayoung Ko, Hyoung‐Joo Kim, Yongjin Lee, Jun‐Hyeong Kim, Michael Alexander, Jonathan R. T. Lakey, Hyunil Kim, Kimyung Choi
    Xenotransplantation.2021;[Epub]     CrossRef
  • Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas
    Adem Y. Dawed, Sook Wah Yee, Kaixin Zhou, Nienke van Leeuwen, Yanfei Zhang, Moneeza K. Siddiqui, Amy Etheridge, Federico Innocenti, Fei Xu, Josephine H. Li, Joline W. Beulens, Amber A. van der Heijden, Roderick C. Slieker, Yu-Chuan Chang, Josep M. Mercade
    Diabetes Care.2021; 44(12): 2673.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal