Deletion of pancreatic β-cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin-induced hyperglycaemia

Makawi Ahmed Abdalhamid Osman, Yu Jing Sun, Rui Jia Li, Hui Lin, Dong Mei Zeng, Xin Yu Chen, Dongfang He, Hui Wei Feng, Zhao Yang, Jin Wang, Chaodong Wu, Min Cui, Jin Peng Sun, Yuqing Huo, Xiao Yu

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Abstract

Severe reduction in the β-cell number (collectively known as the β-cell mass) contributes to the development of both type 1 and type 2 diabetes. Recent pharmacological studies have suggested that increased pancreatic β-cell proliferation could be due to specific inhibition of adenosine kinase (ADK). However, genetic evidence for the function of pancreatic β-cell ADK under physiological conditions or in a pathological context is still lacking. In this study, we crossed mice carrying LoxP-flanked Adk gene with Ins2-Cre mice to acquire pancreatic β -cell ADK deficiency (Ins2-Cre±Adkfl/fl) mice. Our results revealed that Ins2-Cre+/-Adkfl/fl mice showed improved glucose metabolism and β-cell mass in younger mice, but showed normal activity in adult mice. Moreover, Ins2-Cre±Adkfl/fl mice were more resistant to streptozotocin (STZ) induced hyperglycaemia and pancreatic β-cell damage in adult mice. In conclusion, we found that ADK negatively regulates β-cell replication in young mice as well as under pathological conditions, such as STZ induced pancreatic β-cell damage. Our study provided genetic evidence that specific inhibition of pancreatic β-cell ADK has potential for anti-diabetic therapy.

Original languageEnglish (US)
Pages (from-to)4653-4665
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number7
DOIs
StatePublished - Jul 2019

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Keywords

  • adenosine kinase
  • diabetes
  • insulin
  • replication
  • β cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Ahmed Abdalhamid Osman, M., Sun, Y. J., Li, R. J., Lin, H., Zeng, D. M., Chen, X. Y., He, D., Feng, H. W., Yang, Z., Wang, J., Wu, C., Cui, M., Sun, J. P., Huo, Y., & Yu, X. (2019). Deletion of pancreatic β-cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin-induced hyperglycaemia. Journal of Cellular and Molecular Medicine, 23(7), 4653-4665. https://doi.org/10.1111/jcmm.14216