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

Severe reduction in the beta-cell number (collectively known as the beta-cell mass) contributes to the development of both type 1 and type 2 diabetes. Recent pharmacological studies have suggested that increased pancreatic beta-cell proliferation could be due to specific inhibition of adenosine kinase (ADK). However, genetic evidence for the function of pancreatic beta-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 beta-cell ADK deficiency (Ins2-Cre(+/-)Adk(fl/fl)) mice. Our results revealed that Ins2-Cre(+/-)Adk(fl/fl) mice showed improved glucose metabolism and beta-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 beta-cell damage in adult mice. In conclusion, we found that ADK negatively regulates beta-cell replication in young mice as well as under pathological conditions, such as STZ induced pancreatic beta-cell damage. Our study provided genetic evidence that specific inhibition of pancreatic beta-cell ADK has potential for anti-diabetic therapy.