regulating glucose uptake in renal proximal tubules for treating chronic cardiorenal failure.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Kagawa University
• Principal Investigator: Nakano Daisuke 香川大学, 医学部, 准教授 (30524178)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: SGLT2 / GLUT2 / 腎臓 / 糖尿病

Outline of Final Research Achievements

We examined the reno-protective effects of SGLT2 inhibitors and its mechanism. Our data elucidated that the inhibitors for SGLT2 do not suppress the glucose uptake in the healthy proximal tubular cells, and that it does in the injured tubular cells. The kinetics of glucose uptake depends on GLUT2 that could be downregulated by the damage. The cells suppressed extracellular glucose uptake by the combination with cell damage and SGLT2 inhibition, upregulated angiogenic factors, such as VEGFA. This contributed to the reconstruction of capillary network in the kidney. The glucose uptake in the proximal tubules was unaffected even under the hyperglycemic or hypoglycemic condition, by SGLT2 inhibitor treatment.

Free Research Field

薬理学、腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

SGLT2阻害薬は臓器保護効果を示す糖尿病治療薬として注目を集めている。我々は、そのメカニズムの一端が、障害を受けた組織毛細血管網の再構築にあることを見出した。そして、一般的な予想とは異なり、正常細胞における糖取り込みはほとんど影響を受けないこと、障害細胞でのみそれを阻害し、障害軽減機序を活性化することを発見した。