Abstract
The formation of amyloid oligomers and fibrils of the human islet amyloid polypeptide (hIAPP) has been linked with β- cell failure and death which causes the onset, progression, and comorbidities of diabetes. We begin to unpack the aggregation-oligomerization-fibrillization process of these oligomers taken from sera of pediatric patients. The naturally occurring or real hIAPP (not synthetic) amyloid oligomers (RIAO) were successfully isolated, we demonstrated the presence of homo (dodecamers, hexamers, and trimers) and hetero-RIAO, as well as several biophysical characterizations which allow us to learn from the real phenomenon taking place. We found that the aggregation/oligomerization process is active in the sera and showed that it happens very fast. The RIAO can form fibers and react with anti-hIAPP and anti-amyloid oligomers antibodies. Our results opens the epistemic horizon and reveal real differences between the four groups (Controls vs obesity, T1DM or T2DM) accelerating the process of understanding and discovering novel and more efficient prevention, diagnostic, transmission and therapeutic pathways.
Highlights
IntroductionAny event in the universe of protein conformational diseases (PCD) such as Diabetes Mellitus (DM), Alzheimer Disease (AD), and Cancer, among others, is defined by its information (genetics, epigenetics, molecular networks, stress, ageing, etc) which includes the development of micro and macro-environments and network spheres that influence and interact with each other[1,2,3,4]
Any event in the universe of protein conformational diseases (PCD) such as Diabetes Mellitus (DM), Alzheimer Disease (AD), and Cancer, among others, is defined by its information which includes the development of micro and macro-environments and network spheres that influence and interact with each other[1,2,3,4]
We avoid the polymorphism of oligomeric species by concentrating on those oligomers with low molecular weight that are related to cellular apoptosis and may have a role to play in the developing stages of metabolic syndrome and diabetes[26,31,32,56,57]
Summary
Any event in the universe of protein conformational diseases (PCD) such as Diabetes Mellitus (DM), Alzheimer Disease (AD), and Cancer, among others, is defined by its information (genetics, epigenetics, molecular networks, stress, ageing, etc) which includes the development of micro and macro-environments and network spheres that influence and interact with each other[1,2,3,4]. Small hIAPP oligomers with a high surface hydrophobicity formed during the nucleation conformational phase are very toxic, permeate the membrane and produce non-selective pores[19,21,26,28,29,32,40,45,46,47] These form highly ordered fibrils with cross-β structure some aggregates are amorphous assemblies[2,12,16,19,48], the fibers on the surface of the cell membranes are cytotoxic as well by causing the fragmentation of the membrane by micellization[16,40,45,48]; recently was demonstrated that tightly mated β-sheet are relevant for toxicity[24,25,49]. The answers to these questions have implications in the prevention, diagnosis, treatment, prognosis and transmission of DM and PCD in general
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