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 language | English (US) |
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Pages (from-to) | 4653-4665 |
Number of pages | 13 |
Journal | Journal of Cellular and Molecular Medicine |
Volume | 23 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2019 |
Keywords
- adenosine kinase
- diabetes
- insulin
- replication
- β cell
ASJC Scopus subject areas
- Molecular Medicine
- Cell Biology