Early administration of dapagliflozin preserves pancreatic β‐cell mass through a legacy effect in a mouse model of type 2 diabetes

• Main Authors: Ayumi Kanno, Shun‐ichiro Asahara, Mao Kawamura, Ayuko Furubayashi, Shoko Tsuchiya, Emi Suzuki, Tomoko Takai, Maki Koyanagi‐Kimura, Tomokazu Matsuda, Yuko Okada, Wataru Ogawa, Yoshiaki Kido
• Format: Article
• Language: English
• Published: Wiley 2019-05-01
• Series: Journal of Diabetes Investigation
• Subjects: Pancreatic β‐cell; Sodium–glucose cotransporter 2; Type 2 diabetes mellitus
• Online Access: https://doi.org/10.1111/jdi.12945
• ISSN: 2040-1116; 2040-1124

Abstract Aims/Introduction The preservation of pancreatic β‐cell mass is an essential factor in the onset and development of type 2 diabetes mellitus. Recently, sodium–glucose cotransporter 2 inhibitors have been launched as antihyperglycemic agents, and their organ‐protective effects are attracting attention. They are also reported to have favorable effects on the preservation of pancreatic β‐cell mass, but the appropriate timing for the administration of sodium–glucose cotransporter 2 inhibitors is obscure. Materials and Methods In the present study, we administered a sodium–glucose cotransporter 2 inhibitor, dapagliflozin, to an animal model of type 2 diabetes mellitus, db/db mice, and investigated the adequate timing and duration for its administration. We also carried out microarray analysis using pancreatic islets from db/db mice. Results We found that dapagliflozin preserved pancreatic β‐cell mass depending on the duration of administration and markedly improved blood glucose levels. If the duration was the same, the earlier administration of dapagliflozin was more effective in preserving pancreatic β‐cell mass, increasing serum insulin levels and improving blood glucose levels. From microarray analysis, we discovered that the expression of Agr2, Tff2 and Gkn3 was significantly upregulated after the early administration of dapagliflozin. This upregulated gene expression might provide a legacy effect for the preservation of pancreatic β‐cell mass. Conclusions We expect that the early administration of dapagliflozin would provide a long‐lasting effect in preserving pancreatic β‐cell mass.