Islet amyloid polypeptide gene variation (IAPP) and the risk of incident type 2 diabetes mellitus: The women's genome health study

Zee, Robert Y.L.; Pulido‐Perez, Patricia; Pérez-Fuentes, Ricardo; Ridker, Paul M.; Chasman, Daniel I.; Romero, José R.

doi:10.1016/j.cca.2010.12.040

Cited by 3 publications

(2 citation statements)

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“…The self‐assembly of peptides has attracted a great attention due to its association with numerous degenerative diseases (e.g., Alzheimer's, Parkinson's, and type II diabetes) and its potential applications in nanotemplating and bio‐nanotechnology . Human islet amyloid polypeptide (hIAPP), a 37‐residue peptide hormone co‐secreted with insulin by pancreatic β‐cells for glycemic control, is the main component of the amyloid deposits found in the pancreas . Similar to other amyloid deposits, hIAPP amyloid nanofibers displayed a common cross‐β core structure with the β‐strands aligned perpendicularly to the fibril axis .…”

Section: Introductionmentioning

confidence: 99%

Amyloid Self‐Assembly of hIAPP8‐20 via the Accumulation of Helical Oligomers, α‐Helix to β‐Sheet Transition, and Formation of β‐Barrel Intermediates

Sun

Käkinen

Xing

et al. 2019

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The self-assembly of peptides has attracted a great attention due to its association with numerous degenerative diseases (e.g., Alzheimer's, [1] Parkinson's, [1] and type II diabetes [2] ) and itsThe self-assembly of human islet amyloid polypeptide (hIAPP) into β-sheetrich nanofibrils is associated with the pathogeny of type 2 diabetes. Soluble hIAPP is intrinsically disordered with N-terminal residues 8-17 as α-helices. To understand the contribution of the N-terminal helix to the aggregation of full-length hIAPP, here the oligomerization dynamics of the hIAPP fragment 8-20 (hIAPP8-20) are investigated with combined computational and experimental approaches. hIAPP8-20 forms cross-β nanofibrils in silico from isolated helical monomers via the helical oligomers and α-helices to β-sheets transition, as confirmed by transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and reversed-phase high performance liquid chromatography. The computational results also suggest that the critical nucleus of aggregation corresponds to hexamers, consistent with a recent mass-spectroscopy study of hIAPP8-20 aggregation. hIAPP8-20 oligomers smaller than hexamers are helical and unstable, while the α-to-β transition starts from the hexamers. Converted β-sheet-rich oligomers first form β-barrel structures as intermediates before aggregating into cross-β nanofibrils. This study uncovers a complete picture of hIAPP8-20 peptide oligomerization, aggregation nucleation via conformational conversion, formation of β-barrel intermediates, and assembly of cross-β protofibrils, thereby shedding light on the aggregation of full-length hIAPP, a hallmark of pancreatic beta-cell degeneration.

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Section: Introductionmentioning

confidence: 99%

Amyloid Self‐Assembly of hIAPP8‐20 via the Accumulation of Helical Oligomers, α‐Helix to β‐Sheet Transition, and Formation of β‐Barrel Intermediates

Sun

Käkinen

Xing

et al. 2019

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“…TCF7L2 has subsequently been shown to modulate pancreatic islet function (Lyssenko et al, 2007). For amylin itself, promoter variants and specific mutations such as Ser20Gly have been shown to be associated with T2DM in some studies, whereas others showed no association, including one study with over 22,000 participants (Zee et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

Lessons from two prevalent amyloidoses—what amylin and Aβ have in common

Götz¹,

Lim²,

Eckert³

2013

Front. Aging Neurosci.

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The amyloidogenic peptide Aβ plays a key role in Alzheimer's disease (AD) forming insoluble aggregates in the brain. The peptide shares its amyloidogenic properties with amylin that forms aggregates in the pancreas of patients with Type 2 Diabetes mellitus (T2DM). While epidemiological studies establish a link between these two diseases, it is becoming increasingly clear that they also share biochemical features suggesting common pathogenic mechanisms. We discuss commonalities as to how Aβ and amylin deregulate the cellular proteome, how they impair mitochondrial functions, to which receptors they bind, aspects of their clearance and how therapeutic strategies exploit the commonalities between Aβ and amylin. We conclude that research into these two molecules is mutually beneficial for the treatment of AD and T2DM.

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Association of a SNP in the IAPP gene and hyperglycemia on β-cell dysfunction in type 2 diabetes: the Toon Genome Study

et al. 2021

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Islet amyloid polypeptide gene variation (IAPP) and the risk of incident type 2 diabetes mellitus: The women's genome health study

Abstract: Background-Islet amyloid polypeptide (IAPP) gene variation has recently been implicated in type 2 diabetes mellitus (T2D). However, to date, no prospective epidemiological data are available.

Cited by 3 publications

References 10 publications

Amyloid Self‐Assembly of hIAPP8‐20 via the Accumulation of Helical Oligomers, α‐Helix to β‐Sheet Transition, and Formation of β‐Barrel Intermediates

Amyloid Self‐Assembly of hIAPP8‐20 via the Accumulation of Helical Oligomers, α‐Helix to β‐Sheet Transition, and Formation of β‐Barrel Intermediates

Lessons from two prevalent amyloidoses—what amylin and Aβ have in common

Association of a SNP in the IAPP gene and hyperglycemia on β-cell dysfunction in type 2 diabetes: the Toon Genome Study

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