Islet amyloid polypeptide, a 37 residue polypeptide, is the main protein component of islet amyloid deposits produced in the pancreas in type 2 diabetes.
The human islet amyloid polypeptide (hIAPP) or amylin is the major constituent of amyloidogenic aggregates found in pancreatic islets of type 2 diabetic patients that have been associated with β-cell dysfunction and/or death associated with type 2 diabetes mellitus (T2DM).
Here, we report the direct interaction of an AD-associated amyloidogenic cytotoxic fragment of Tau (R3:306-336) with islet amyloid polypeptide (IAPP) implicated in T2D.
If hIAPP aggregation into toxic amyloid is on-path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease.
Further in vivo zebrafish embryonic assay indicated improved survival and hatching, as well as decreased frequency and severity of developmental abnormalities for embryos treated with the heteroaggregates of IAPP with 19-29 S20G, but not with 8-20, compared to the control, indicating the therapeutic potential of 19-29 S20G against T2D.
Type 2 diabetes mellitus (T2DM) is characterized by the dysfunction and loss of pancreatic islet β‑cells, in part due to islet amyloid deposits derived from islet amyloid polypeptide (IAPP).
In this study, we aim to elucidate the impact of protein glycation on islet amyloid polypeptide (IAPP, also known as amylin) aggregation, which was strongly associated with T2D.
Human islet amyloid polypeptide (hIAPP, amylin) may self-aggregate and rupture the membrane of β cells, which is closely correlated with the pathogenesis of type 2 diabetes mellitus (T2DM).
In contrast to rodent amylin, human amylin is prone to form amyloidogenic aggregates, proposed to play a role in the pathogenesis of Type 2 Diabetes by impairing β-cell functionality.
The presence of both tau and Aβ inclusions in pancreatic β cells, and of amylin deposits in the brain, provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of T2DM and AD.ANN NEUROL 2019;86:539-551.
The islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone whose deposition as amyloid fibrils in the pancreatic islets is associated with type 2 diabetes.
In humans, β-amyloid and islet amyloid polypeptide (IAPP, also known as amylin) aggregations are linked to Alzheimer's disease and type-2 diabetes, respectively.
Type 2 diabetes mellitus (T2Dm) is a neurodegenerative disease, which occurs due to the self-association of human islet amyloid polypeptide (hIAPP), also known as human amylin.
Inflammatory cascades in both tissues are triggered by the uptake of β-amyloid peptide (Aβ) or islet amyloid polypeptide (IAPP) aggregates by microglial cells (AD) or macrophages (T2D) and their insufficient lysosomal degradation.