박병현 (KAIST)

한빛사논문

조회333

KAIST

CV File 149 kb

Nat. Commun., Aug 10 2024, 15 (1) | https://doi.org/10.1038/s41467-024-51240-w PAK4 phosphorylates and inhibits AMPKα to control glucose uptake

Dandan Wu ¹, Hwang Chan Yu ², Hye-Na Cha³, Soyoung Park ³, Yoonji Lee ⁴, Sun-Jung Yoon ⁵, So-Young Park ^3,*, Byung-Hyun Park ^2,*& Eun Ju Bae ^1,*

¹School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, Jeonju 54896, Republic of Korea.
²Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejon 34141, Republic of Korea.
³Department of Physiology, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea.
⁴College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
⁵Department of Orthopedic Surgery, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea.

^*Corresponding authors: correspondence to So-Young Park, Byung-Hyun Park or Eun Ju Bae

Abstract

Our recent studies have identified p21-activated kinase 4 (PAK4) as a key regulator of lipid catabolism in the liver and adipose tissue, but its role in glucose homeostasis in skeletal muscle remains to be explored. In this study, we find that PAK4 levels are highly upregulated in the skeletal muscles of diabetic humans and mice. Skeletal muscle-specific Pak4 ablation or administering the PAK4 inhibitor in diet-induced obese mice retains insulin sensitivity, accompanied by AMPK activation and GLUT4 upregulation. We demonstrate that PAK4 promotes insulin resistance by phosphorylating AMPKα2 at Ser491, thereby inhibiting AMPK activity. We additionally show that skeletal muscle-specific expression of a phospho-mimetic mutant AMPKα2^S491D impairs glucose tolerance, while the phospho-inactive mutant AMPKα2^S491A improves it. In summary, our findings suggest that targeting skeletal muscle PAK4 may offer a therapeutic avenue for type 2 diabetes.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-13)
연구진국내 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기