Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus

Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus

Hye Rin Jeong, Seong Soo A AnDepartment of Bionano Technology, Gachon Medical Research Institute, Gachon University, Gyeonggi-do, Republic of KoreaAbstract: Human islet amyloid polypeptide (h-IAPP) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic...

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Autores principales: Jeong HR, An SSA
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
Materias:
Amyloid aggregation
Causative factor
IAPP (Islet Amyloid Polypeptide)
Toxic oligomer
T2DM (Type2 Diabetes Mellitus)
Geriatrics
RC952-954.6
Acceso en línea:https://doaj.org/article/cdac1a039845484d8784430668ce337a
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spelling oai:doaj.org-article:cdac1a039845484d8784430668ce337a2021-12-02T02:12:24ZCausative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus1178-1998https://doaj.org/article/cdac1a039845484d8784430668ce337a2015-11-01T00:00:00Zhttps://www.dovepress.com/causative-factors-for-formation-of-toxic-islet-amyloid-polypeptide-oli-peer-reviewed-article-CIAhttps://doaj.org/toc/1178-1998Hye Rin Jeong, Seong Soo A AnDepartment of Bionano Technology, Gachon Medical Research Institute, Gachon University, Gyeonggi-do, Republic of KoreaAbstract: Human islet amyloid polypeptide (h-IAPP) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic β-cells. Recently, h-IAPP was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus (T2DM). Since the causative factors of IAPP (or amylin) oligomer aggregation are not fully understood, this review will discuss the various forms of h-IAPP aggregation. Not all forms of IAPP aggregates trigger the destruction of β-cell function and loss of β-cell mass; however, toxic oligomers do trigger these events. Once these toxic oligomers form under abnormal metabolic conditions in T2DM, they can lead to cell disruption by inducing cell membrane destabilization. In this review, the various factors that have been shown to induce toxic IAPP oligomer formation will be presented, as well as the potential mechanism of oligomer and fibril formation from pro-IAPPs. Initially, pro-IAPPs undergo enzymatic reactions to produce the IAPP monomers, which can then develop into oligomers and fibrils. By this mechanism, toxic oligomers could be generated by diverse pathway components. Thus, the interconnections between factors that influence amyloid aggregation (eg, absence of PC2 enzyme, deamidation, reduction of disulfide bonds, environmental factors in the cell, genetic mutations, copper metal ions, and heparin) will be presented. Hence, this review will aid in understanding the fundamental causative factors contributing to IAPP oligomer formation and support studies for investigating novel T2DM therapeutic approaches, such as the development of inhibitory agents for preventing oligomerization at the early stages of diabetic pathology.Keywords: amyloid aggregation, causative factor, IAPP, islet amyloid polypeptide, toxic oligomer, T2DM, type 2 diabetes mellitusJeong HRAn SSADove Medical PressarticleAmyloid aggregationCausative factorIAPP (Islet Amyloid Polypeptide)Toxic oligomerT2DM (Type2 Diabetes Mellitus)GeriatricsRC952-954.6ENClinical Interventions in Aging, Vol Volume 10, Pp 1873-1879 (2015)
institution DOAJ
collection DOAJ
language EN
topic Amyloid aggregation
Causative factor
IAPP (Islet Amyloid Polypeptide)
Toxic oligomer
T2DM (Type2 Diabetes Mellitus)
Geriatrics
RC952-954.6
spellingShingle Amyloid aggregation
Causative factor
IAPP (Islet Amyloid Polypeptide)
Toxic oligomer
T2DM (Type2 Diabetes Mellitus)
Geriatrics
RC952-954.6
Jeong HR
An SSA
Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
description Hye Rin Jeong, Seong Soo A AnDepartment of Bionano Technology, Gachon Medical Research Institute, Gachon University, Gyeonggi-do, Republic of KoreaAbstract: Human islet amyloid polypeptide (h-IAPP) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic β-cells. Recently, h-IAPP was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus (T2DM). Since the causative factors of IAPP (or amylin) oligomer aggregation are not fully understood, this review will discuss the various forms of h-IAPP aggregation. Not all forms of IAPP aggregates trigger the destruction of β-cell function and loss of β-cell mass; however, toxic oligomers do trigger these events. Once these toxic oligomers form under abnormal metabolic conditions in T2DM, they can lead to cell disruption by inducing cell membrane destabilization. In this review, the various factors that have been shown to induce toxic IAPP oligomer formation will be presented, as well as the potential mechanism of oligomer and fibril formation from pro-IAPPs. Initially, pro-IAPPs undergo enzymatic reactions to produce the IAPP monomers, which can then develop into oligomers and fibrils. By this mechanism, toxic oligomers could be generated by diverse pathway components. Thus, the interconnections between factors that influence amyloid aggregation (eg, absence of PC2 enzyme, deamidation, reduction of disulfide bonds, environmental factors in the cell, genetic mutations, copper metal ions, and heparin) will be presented. Hence, this review will aid in understanding the fundamental causative factors contributing to IAPP oligomer formation and support studies for investigating novel T2DM therapeutic approaches, such as the development of inhibitory agents for preventing oligomerization at the early stages of diabetic pathology.Keywords: amyloid aggregation, causative factor, IAPP, islet amyloid polypeptide, toxic oligomer, T2DM, type 2 diabetes mellitus
format article
author Jeong HR
An SSA
author_facet Jeong HR
An SSA
author_sort Jeong HR
title Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
title_short Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
title_full Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
title_fullStr Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
title_full_unstemmed Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
title_sort causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/cdac1a039845484d8784430668ce337a
work_keys_str_mv AT jeonghr causativefactorsforformationoftoxicisletamyloidpolypeptideoligomerintype2nbspdiabetesmellitus
AT anssa causativefactorsforformationoftoxicisletamyloidpolypeptideoligomerintype2nbspdiabetesmellitus
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