Open AccessDeletion of pancreatic β‐cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin‐induced hyperglycaemia
Author(s) -
Ahmed Abdalhamid Osman Makawi,
Sun YuJing,
Li RuiJia,
Lin Hui,
Zeng DongMei,
Chen XinYu,
He Dongfang,
Feng HuiWei,
Yang Zhao,
Wang Jin,
Wu Chaodong,
Cui Min,
Sun JinPeng,
Huo Yuqing,
Yu Xiao
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14216
Subject(s) - streptozotocin , glucose homeostasis , adenosine kinase , endocrinology , medicine , cell , context (archaeology) , adenosine , biology , diabetes mellitus , adenosine deaminase , insulin resistance , biochemistry , paleontology
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 ± Adk fl/fl ) mice. Our results revealed that Ins2‐Cre +/‐ Adk fl/fl mice showed improved glucose metabolism and β‐cell mass in younger mice, but showed normal activity in adult mice. Moreover, Ins2‐Cre ± Adk fl/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.