An Autophagy Enhancer Ameliorates Diabetes of Human IAPP-transgenic Mice Through Clearance of Amyloidogenic Oligomer

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 9

PMID 33420039

Citations 34

Authors

Jinyoung Kim

Kihyoun Park

Min Jung Kim

Hyejin Lim

Kook Hwan Kim

Sun-Woo Kim

Eun-Seo Lee

Hyongbum Henry Kim

Sung Joo Kim

Kyu Yeon Hur

Jae Hyeon Kim

Jin Hee Ahn

Kun-Ho Yoon

Ji-Won Kim

Myung-Shik Lee

Affiliations

Soon will be listed here.

Abstract

We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.

Citing Articles

Decoding the Contribution of IAPP Amyloid Aggregation to Beta Cell Dysfunction: A Systematic Review and Epistemic Meta-Analysis of Type 1 Diabetes.

Moya-Gudino V, Altamirano-Bustamante N, Revilla-Monsalve C, Altamirano-Bustamante M Int J Mol Sci. 2025; 26(2).

PMID: 39859479 PMC: 11766435. DOI: 10.3390/ijms26020767.

Pharmaceutical Agents for Targeting Autophagy and Their Applications in Clinics.

Kench U, Sologova S, Smolyarchuk E, Prassolov V, Spirin P Pharmaceuticals (Basel). 2024; 17(10).

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A Review of Animal Models for Studying Bone Health in Type-2 Diabetes Mellitus (T2DM) and Obesity.

Norazman S, Mohd Zaffarin A, Shuid A, Hassan H, Soleiman I, Kuan W Int J Mol Sci. 2024; 25(17).

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Dysregulation of pancreatic β-cell autophagy and the risk of type 2 diabetes.

Al-Kuraishy H, Jabir M, Al-Gareeb A, Klionsky D, Albuhadily A Autophagy. 2024; 20(11):2361-2372.

PMID: 38873924 PMC: 11572262. DOI: 10.1080/15548627.2024.2367356.

Inhibition of Insulin Secretion Induces Golgi Morphological Changes.

Iwamoto T, Shimizu S, Tajima-Sakurai H, Yamaguchi H, Nishida Y, Arakawa S Juntendo Iji Zasshi. 2024; 69(1):42-49.

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