Startseite Human islet amyloid polypeptide (hIAPP) - a curse in type II diabetes mellitus: insights from structure and toxicity studies
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Human islet amyloid polypeptide (hIAPP) - a curse in type II diabetes mellitus: insights from structure and toxicity studies

  • Ajit Kumar Bishoyi , Pratiksha H. Roham , Kavitha Rachineni , Shreyada Save , M. Asrafuddoza Hazari , Shilpy Sharma EMAIL logo und Ashutosh Kumar EMAIL logo
Veröffentlicht/Copyright: 4. September 2020

Abstract

The human islet amyloid polypeptide (hIAPP) or amylin, a neuroendocrine peptide hormone, is known to misfold and form amyloidogenic aggregates that have been observed in the pancreas of 90% subjects with Type 2 Diabetes Mellitus (T2DM). Under normal physiological conditions, hIAPP is co-stored and co-secreted with insulin; however, under chronic hyperglycemic conditions associated with T2DM, the overexpression of hIAPP occurs that has been associated with the formation of amyloid deposits; as well as the death and dysfunction of pancreatic β-islets in T2DM. Hitherto, various biophysical and structural studies have shown that during this process of aggregation, the peptide conformation changes from random structure to helix, then to β-sheet, subsequently to cross β-sheets, which finally form left-handed helical aggregates. The intermediates, formed during this process, have been shown to induce higher cytotoxicity in the β-cells by inducing cell membrane disruption, endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, islet inflammation, and DNA damage. As a result, several research groups have attempted to target both hIAPP aggregation phenomenon and the destabilization of preformed fibrils as a therapeutic intervention for T2DM management. In this review, we have summarized structural aspects of various forms of hIAPP viz. monomer, oligomers, proto-filaments, and fibrils of hIAPP. Subsequently, cellular toxicity caused by toxic conformations of hIAPP has been elaborated upon. Finally, the need for performing structural and toxicity studies in vivo to fill in the gap between the structural and cellular aspects has been discussed.


Corresponding author: Ashutosh Kumar, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, Maharashtra, India, E-mail: ; and Shilpy Sharma, Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, 411007, Maharashtra, India, E-mail:
Ajit Kumar Bishoyi, Pratiksha H. Roham, and Kavitha Rachineni contributed equally to this article.

Award Identifier / Grant number: BT/RLF/Re-entry/11/2012

Award Identifier / Grant number: EMR/2016/002798

Award Identifier / Grant number: (09/137/06.2) 2019 EMR-I

Award Identifier / Grant number: F.4-5(18-FRP)(IV-Cycle)/2017(BSR)

Funding source: Wadhwani Research center for Bioengineering (Wadhwani Research Foundation)

Award Identifier / Grant number: RD/0118-DONWR04-001

Acknowledgments

A.K. and S.S. acknowledge funding from the Wadhwani research foundation (Wadhwani Research centre for Bioengineering). S.S. acknowledges funding from Ramalingaswami fellowship (BT/RLF/Re-entry/11/2012; Department of Biotechnology-DBT, Government of India); and University Grants Commission (UGC, Government of India F.4-5(18-FRP) (IV-Cycle)/2017(BSR)). S.S. laboratory has been generously supported by Research and Development grant to the Department of Biotechnology, SPPU; and UPE Phase II and RUSA 2.0 grants to SPPU. P.H.R. acknowledges CSIR-SRF, GOI ((09/137/06.2) 2019 EMR-I) for her SRF fellowship and S.N.S. acknowledges Wadhwani research foundation for her project assistant fellowship. K.R. is supported by the Institute postdoctoral fellowship of IIT Bombay. A.K.B. acknowledges the Department of Science and Technology (DST) for his financial assistant from DST-JRF.

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was supported by funds obtained from Wadhwani research foundation (Wadhwani Research centre for Bioengineering); Department of Biotechnology (BT/RLF/Re-entry/11/2012); University Grants Commission (F.4-5(18-FRP) (IV-Cycle)/2017(BSR)); and Department of Science and Technology.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2020-04-30
Accepted: 2020-08-11
Published Online: 2020-09-04
Published in Print: 2021-01-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 14.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2020-0174/pdf
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