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