Insulin Modulated Self-Assembled Nanostructures of IAPP Under Amyloid Disease State

Autor: Mysore Sridhar Santosh, Chunchanakuppe Renukaprasad Ravi Kumar, Madhihalli Basavaraju Divakara, Narendra Reddy
Rok vydání: 2018
Předmět:
Zdroj: Advanced Science Letters. 24:5742-5747
ISSN: 1936-6612
DOI: 10.1166/asl.2018.12189
Popis: Insulin resistance is considered to be the most common cause of type 2 diabetes (T2D) wherein pancreatic β-cells cosecrete islet amyloid polypeptide (IAPP) with insulin and forms amyloid fibrils at low concentrations. Localization of IAPP between the secretory vesicle membrane and the crystal inhibits IAPP fibrillation. Moreover, inhibition of monomeric insulin and lipid membranes accelerate the fibrillation of IAPP in vitro. The present work investigates the interactions in vitro between lipid-IAPP-insulin under amyloid disease state. Fluorescence microscopy is used to investigate insulin’s effect on fibrillation of IAPP and to study the interactions of crystalline insulin with lipids and IAPP but revealed no significant interaction between IAPP and insulin. However, stable insulin-IAPP interactions are apparent in larger assemblies of crystalline insulin or IAPP fibres favouring the chances of various physiological interactions between these two β-cell hormones. The atomic force microscopy and electron microscopy studies indicate that the assembling process of hIAPP fibre can be tuned by the large surface of insulin. Also, the morphology of self-assembled nanostructures of hIAPP is modulated by the effect of insulin. These results are expected to offer a greater understanding of the interactions between insulin, lipids and peptides paving new dimensions in amyloid disease based therapeutics.
Databáze: OpenAIRE