The role of Protein Tyrosine Phosphatase 1B in AgRP neurons

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18005
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Nagoya University
• Principal Investigator: Sugiyama Mariko 名古屋大学, 医学部附属病院, 助教 (70823540)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: PTP1B / AgRP / POMC / レプチン

Outline of Final Research Achievements

For the purpose of elucidating the mechanisms of the hypoglycemic effect of leptin in type 1 diabetes model (IDDM) mice, we generated mice lacking Protein Tyrosine Phosphatase 1B specifically in AgRP or POMC neurons, and administered streptozotocin intraperitoneally to generate IDDM mice. After the mice were prepared, the effect of peripheral administration of leptin on glucose metabolism was examined. In AgRP KO mice, the hypoglycemic effect of leptin was only slightly observed compared to the wild type, but in POMC KO mice, the hypoglycemic effect was confirmed to be significant compared to the wild type.

Free Research Field

医歯薬学　内科系臨床医学・代謝学

Academic Significance and Societal Importance of the Research Achievements

抗PTP1B薬はインスリン、レプチンシグナルを改善する薬剤として糖尿病治療薬として臨床治験中である。本研究ではIDDMモデルマウスにおいて、中枢において糖代謝を司るPOMCおよびAgRPニューロン特異的にPTP1Bを欠損させたモデルマウスを用いて糖代謝を評価した。本研究の結果は抗PTP1B薬の作用機序の解明に寄与し、また治療選択肢の乏しいIDDM患者において新たな治療戦略の提示につながり社会的な貢献は大きい。