Insulin–eukaryotic model membrane interaction: Mechanistic insight of insulin fibrillation and membrane disruption
| Autor: | Dong Kuk Lee, Anirban Bhunia, Min-Soo Kim, Bhisma N Ratha, Kanchan Garai, Bankanidhi Sahoo |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Fibrillation Chemistry Dye leakage Amyloidosis Insulin medicine.medical_treatment Biophysics Fluorescence correlation spectroscopy Cell Biology Nuclear magnetic resonance spectroscopy medicine.disease Biochemistry 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Membrane Membrane interaction medicine medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1860:1917-1926 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/j.bbamem.2018.02.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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