Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Insulin-eukaryotic Model Membrane Interaction: Mechanistic Insight Of Insulin Fibrillation And Membrane Disruption.

B. N. Ratha, M. Kim, B. Sahoo, K. Garai, Dongkuk Lee, A. Bhunia
Published 2018 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Injection of exogenous insulin in the subcutaneous mass has been a proven therapy for type II diabetes. However, chronic administration of insulin often develops local amyloidosis at the injection site, pathologically known as "Insulin Ball". This reduces the insulin bioavailability and exacerbates the disease pathology. Thus, the molecular interaction between insulin and the recipient's membrane surface plays a co-operative role in accelerating the amyloidosis. This interaction, however, is different from the molecular interaction of insulin with the native membranous environment of the pancreatic β-cells. The differential membrane mediated interaction that directly affects the aggregation kinetics of insulin remains elusive yet intriguing to understand the mechanism of pathological development. In this study we have characterized the interactions of insulin at different states with model eukaryotic membranes using high and low-resolution spectroscopic techniques in combination with microscopic investigation. Our results show that insulin amyloid intermediates are capable of interacting with model membranes with variable functional affinity towards the different compositions. Fluorescence correlation spectroscopy confirms the aggregation states of insulin in presence of the eukaryotic model membranes while solid-state NMR spectroscopy in conjugation with differential scanning calorimetry elucidates the molecular interaction of insulin intermediates with the lipid head groups along with the acyl chains. Additionally, dye leakage assays support the eukaryotic model membrane disruption by insulin intermediates, similar to hIAPP and Aβ40, as previously reported. Thus, the present study establishes the distinct mode of interactions of insulin amyloid with pancreatic β-cell and general mammalian cell mimicking membranes.
This paper references
10.2337/diacare.13.9.911
Insulin Administration via Liposomes
R. S. Spangler (1990)
10.1016/j.bpc.2010.01.006
Suppression of IAPP fibrillation at anionic lipid membranes via IAPP-derived amyloid inhibitors and insulin.
D. Sellin (2010)
10.1016/S0076-6879(99)09048-5
Inflammatory responses to amyloid fibrils.
S. Yates (1999)
10.1111/j.1365-2230.2012.04373.x
Coexistence of insulin‐derived amyloidosis and an overlying acanthosis nigricans‐like lesion at the site of insulin injection
S. Kudo-Watanuki (2013)
10.1073/pnas.142459399
The protofilament structure of insulin amyloid fibrils
J. L. Jimenez (2002)
10.1529/BIOPHYSJ.106.098608
A three-stage kinetic model of amyloid fibrillation.
C. Lee (2007)
10.1016/j.bpj.2010.09.070
Biphasic effects of insulin on islet amyloid polypeptide membrane disruption.
J. Brender (2011)
10.1016/j.nbd.2006.04.015
Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons
A. Schneider (2006)
10.1016/S0306-4522(00)00391-2
Amyloid-like inclusions in Huntington’s disease
D. P. McGowan (2000)
10.1016/j.amjmed.2013.10.029
Insulin-derived amyloidosis and poor glycemic control: a case series.
T. Nagase (2014)
10.2169/INTERNALMEDICINE.49.2633
Localized amyloidosis at the site of repeated insulin injection in a diabetic patient.
Y. Shikama (2010)
10.1016/S0140-6736(09)60041-6
The insulin ball
T. Nagase (2009)
10.1529/BIOPHYSJ.103.038828
NMR Studies of lipid lateral diffusion in the DMPC/gramicidin D/water system: peptide aggregation and obstruction effects.
G. Oraedd (2004)
10.1002/ajh.23334
Localized insulin‐derived amyloidosis: A potential pitfall in the diagnosis of systemic amyloidosis by fat aspirate
A. D’Souza (2012)
10.1111/j.1365-2230.2009.03711.x
Localized cutaneous amyloid at an insulin injection site
A. A. Lonsdale-Eccles (2009)
10.7554/eLife.19273
Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity
P. Krotee (2017)
10.1016/j.ejmech.2016.02.065
Structure of amyloid oligomers and their mechanisms of toxicities: Targeting amyloid oligomers using novel therapeutic approaches.
Parveen Salahuddin (2016)
10.1186/s12951-015-0136-y
Nanoparticle based insulin delivery system: the next generation efficient therapy for Type 1 diabetes
G. Sharma (2015)
10.1074/jbc.M116.742460
Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic Heptapeptide
B. N. Ratha (2016)
10.1111/j.2042-7158.2011.01369.x
Microneedles: an emerging transdermal drug delivery system
Shital H. Bariya (2012)
10.3109/10717544.2015.1052863
A review of biodegradable polymeric systems for oral insulin delivery
Y. Luo (2016)
10.3109/13506129.2013.876984
Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration
A. D’Souza (2014)
10.1101/cshperspect.a023648
The Amyloid Phenomenon and Its Links with Human Disease.
C. Dobson (2017)
10.1177/193229681200600209
Intrinsic Fibrillation of Fast-Acting Insulin Analogs
R. Woods (2012)
10.1155/2015/849017
The Effects of Lipid Membranes, Crowding and Osmolytes on the Aggregation, and Fibrillation Propensity of Human IAPP
Mimi Gao (2015)
10.1016/j.bpj.2016.08.032
Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans.
A. Datta (2016)
10.1074/jbc.M114.592527
Small Liposomes Accelerate the Fibrillation of Amyloid β (1–40)*
Mayu S. Terakawa (2014)
10.1016/j.bbamem.2014.04.011
Fibrillation of β amyloid peptides in the presence of phospholipid bilayers and the consequent membrane disruption.
W. Qiang (2015)
10.1021/ja802210u
Nitrogen-14 solid-state NMR spectroscopy of aligned phospholipid bilayers to probe peptide-lipid interaction and oligomerization of membrane associated peptides.
A. Ramamoorthy (2008)
10.1016/J.CHEMPHYSLIP.2007.05.006
The effects of various membrane physical-chemical properties on the aggregation kinetics of insulin.
Stefan Grudzielanek (2007)
10.1016/j.bpj.2016.05.050
The Role of Cholesterol in Driving IAPP-Membrane Interactions.
M. F. Sciacca (2016)
10.2174/1872211308666140527143407
Recent advances in the oral delivery of insulin.
Rekha M Ramesan (2014)
10.1016/j.bbapap.2010.04.001
Molecular mechanism of Thioflavin-T binding to amyloid fibrils.
Matthew Biancalana (2010)
10.1016/S0006-3495(03)75006-1
Measuring size distribution in highly heterogeneous systems with fluorescence correlation spectroscopy.
P. Sengupta (2003)
10.1021/acs.biochem.6b01016
Islet Amyloid Polypeptide Membrane Interactions: Effects of Membrane Composition.
Xiaoxue Zhang (2017)
10.1016/S0005-2736(03)00025-7
Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alzheimer's disease.
W. Gibson Wood (2003)
10.1016/j.neurobiolaging.2005.04.017
Common mechanisms of amyloid oligomer pathogenesis in degenerative disease
C. Glabe (2006)
10.1016/j.bbadis.2010.02.008
Amyloid fibrillation and cytotoxicity of insulin are inhibited by the amphiphilic surfactants.
S. S. Wang (2010)
10.4103/2230-8210.146879
Insulin-derived amyloidosis
Y. Gupta (2015)
10.1016/S0006-291X(84)80190-4
Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
G. Glenner (1984)
10.1039/c3cp44696d
Membrane disordering is not sufficient for membrane permeabilization by islet amyloid polypeptide: studies of IAPP(20-29) fragments.
J. Brender (2013)
10.1006/JMBI.1996.0648
Mapping the functional surface of insulin by design: structure and function of a novel A-chain analogue.
Q. Hua (1996)
10.1016/j.bbr.2016.08.002
Early effects of Aβ1-42 oligomers injection in mice: Involvement of PI3K/Akt/GSK3 and MAPK/ERK1/2 pathways
F. Morroni (2016)
10.1002/anie.201409050
Influence of the β-sheet content on the mechanical properties of aggregates during amyloid fibrillization.
F. S. Ruggeri (2015)
10.2174/138920311795860151
Small molecule fluorescent probes for the detection of amyloid self-assembly in vitro and in vivo.
C. Bertoncini (2011)
10.1039/c3cs60431d
Differences between amyloid-β aggregation in solution and on the membrane: insights into elucidation of the mechanistic details of Alzheimer's disease.
S. A. Kotler (2014)
10.1016/j.humpath.2009.02.019
Localized insulin-derived amyloidosis in patients with diabetes mellitus: a case report.
Saniye Yumlu (2009)
10.1016/j.bpj.2011.11.012
Fluorescence correlation spectroscopy: past, present, future.
E. Elson (2011)
10.1007/s00249-015-1019-8
Effect of acidic and basic pH on Thioflavin T absorbance and fluorescence
Ellen V. Hackl (2015)
10.1021/BI00236A025
Comparative 2D NMR studies of human insulin and des-pentapeptide insulin: sequential resonance assignment and implications for protein dynamics and receptor recognition.
Q. Hua (1991)
10.1021/BI963038Q
Mechanisms of stabilization of the insulin hexamer through allosteric ligand interactions.
S. Rahuel-Clermont (1997)
10.1021/bi201871r
Characterization of early stage intermediates in the nucleation phase of Aβ aggregation.
Jiali Zhai (2012)
10.1111/dme.13137
Localized insulin amyloidosis with use of concentrated insulin: a potential complication
A. Mangla (2016)
10.1016/j.febslet.2015.08.013
Cholesterol facilitates interactions between α‐synuclein oligomers and charge‐neutral membranes
Andreas van Maarschalkerweerd (2015)
10.1002/BIES.20151
Insulin and its receptor: structure, function and evolution
P. D. Meyts (2004)
10.1021/BI00231A015
Bilayers of arachidonic acid containing phospholipids studied by 2H and 31P NMR spectroscopy.
K. Rajamoorthi (1991)
10.1136/jnnp.3.3.211
ALZHEIMER'S DISEASE
W. Mcmenemey (1940)
10.1016/j.cell.2012.02.022
The Amyloid State of Proteins in Human Diseases
D. Eisenberg (2012)
10.1021/JP051385G
Thermotropic phase transition in soluble nanoscale lipid bilayers.
I. Denisov (2005)
10.1021/acs.biochem.5b01168
Stabilization of α-Synuclein Fibril Clusters Prevents Fragmentation and Reduces Seeding Activity and Toxicity.
Huy T Lam (2016)
10.1073/pnas.0708354105
Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane
Maarten F. M. Engel (2008)
10.1016/j.colsurfb.2011.11.036
Modulation of pathway of insulin fibrillation by a small molecule helix inducer 2,2,2-trifluoroethanol.
V. Banerjee (2012)
10.1007/978-1-62703-275-9_16
Solid-state NMR approaches to study protein structure and protein-lipid interactions.
C. Aisenbrey (2013)
10.1038/sj.cdd.4400432
Fatal attractions: abnormal protein aggregation and neuron death in Parkinson's disease and Lewy body dementia
J. Trojanowski (1998)
10.1089/ars.2015.6343
Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease
E. Deas (2016)



This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar