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A crucial role of adenosine deaminase in regulating gluconeogenesis in mice.
Ding, Zhao; Ge, Wenhao; Xu, Xiaogang; Xu, Xiaodong; Sun, Qi; Xu, Xi; Zhang, Jianfa.
Affiliation
  • Ding Z; Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
  • Ge W; Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
  • Xu X; Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
  • Xu X; Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
  • Sun Q; Department of Physiology, Bengbu Medical University, Bengbu, China.
  • Xu X; Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China.
  • Zhang J; Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing, China. Electronic address: jfzhang@mail.njust.edu.cn.
J Biol Chem ; 300(7): 107425, 2024 Jul.
Article in En | MEDLINE | ID: mdl-38823639
ABSTRACT
Adenosine deaminase (ADA) catalyzes the irreversible deamination of adenosine (ADO) to inosine and regulates ADO concentration. ADA ubiquitously expresses in various tissues to mediate ADO-receptor signaling. A significant increase in plasma ADA activity has been shown to be associated with the pathogenesis of type 2 diabetes mellitus. Here, we show that elevated plasma ADA activity is a compensated response to high level of ADO in type 2 diabetes mellitus and plays an essential role in the regulation of glucose homeostasis. Supplementing with more ADA, instead of inhibiting ADA, can reduce ADO levels and decrease hepatic gluconeogenesis. ADA restores a euglycemic state and recovers functional islets in db/db and high-fat streptozotocin diabetic mice. Mechanistically, ADA catabolizes ADO and increases Akt and FoxO1 phosphorylation independent of insulin action. ADA lowers blood glucose at a slower rate and longer duration compared to insulin, delaying or blocking the incidence of insulinogenic hypoglycemia shock. Finally, ADA suppresses gluconeogenesis in fasted mice and insulin-deficient diabetic mice, indicating the ADA regulating gluconeogenesis is a universal biological mechanism. Overall, these results suggest that ADA is expected to be a new therapeutic target for diabetes.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Adenosine Deaminase / Diabetes Mellitus, Experimental / Diabetes Mellitus, Type 2 / Gluconeogenesis Limits: Animals Language: En Journal: J Biol Chem Year: 2024 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Adenosine Deaminase / Diabetes Mellitus, Experimental / Diabetes Mellitus, Type 2 / Gluconeogenesis Limits: Animals Language: En Journal: J Biol Chem Year: 2024 Document type: Article Affiliation country: