Department of Physiology and Pathophysiology, Shandong University School of Basic Medical Sciences, Jinan, Shandong, China.
Department of Physiology, Faculty of Medicine and Health Sciences, University of Dongola, Dongola, Sudan.
J Cell Mol Med. 2019 Jul;23(7):4653-4665. doi: 10.1111/jcmm.14216. Epub 2019 May 1.
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 ) mice. Our results revealed that Ins2-Cre Adk mice showed improved glucose metabolism and β-cell mass in younger mice, but showed normal activity in adult mice. Moreover, Ins2-Cre Adk 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.
β细胞数量（统称为β细胞质量）的严重减少导致 1 型和 2 型糖尿病的发展。最近的药理学研究表明，胰腺β细胞增殖的增加可能是由于腺苷激酶（ADK）的特异性抑制。然而，在生理条件下或在病理情况下，胰腺β细胞 ADK 的功能的遗传证据仍然缺乏。在这项研究中，我们将带有 LoxP 侧翼 Adk 基因的小鼠与 Ins2-Cre 小鼠杂交，以获得胰腺β细胞 ADK 缺乏（Ins2-Cre Adk）小鼠。我们的结果表明，Ins2-Cre Adk 小鼠在年轻小鼠中表现出改善的葡萄糖代谢和β细胞质量，但在成年小鼠中表现出正常的活动。此外，Ins2-Cre Adk 小鼠对链脲佐菌素（STZ）诱导的成年小鼠高血糖和胰腺β细胞损伤更具抵抗力。总之，我们发现 ADK 负调控年轻小鼠以及病理条件下（如 STZ 诱导的胰腺β细胞损伤）的β细胞复制。我们的研究提供了遗传证据，表明特异性抑制胰腺β细胞 ADK 具有抗糖尿病治疗的潜力。
