Record Details

Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights

DSpace at IIT Bombay

View Archive Info
 
 
Field Value
 
Title Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights
 
Creator CHOUDHARY, S
KISHORE, N
HOSUR, RV
 
Subject AMYLOID FIBRILS
BOVINE INSULIN
COMPATIBLE SOLUTE
PROTEIN STABILITY
IN-VITRO
AGGREGATION
STABILIZATION
KINETICS
DISEASE
FIBRILLOGENESIS
 
Description We have studied here using a number of biophysical tools the effects of osmolytes, betaine, citrulline, proline and sorbitol which differ significantly in terms of their physical characteristics such as, charge distribution, polarity, H-bonding abilities etc, on the fibrillation of insulin. Among these, betaine, citrulline, and proline are very effective in decreasing the extent of fibrillation. Proline also causes a substantial delay in the onset of fibrillation in the concentration range (50-250 mM) whereas such an effect is seen for citrulline only at 250 mM, and in case of betaine this effect is not seen at all in the whole concentration range. The enthalpies of interaction at various stages of fibrillation process have suggested that the preferential exclusion of the osmolyte and its polar interaction with the protein are important in inhibition. The results indicate that the osmolytes are most effective when added prior to the elongation stage of fibrillation. These observations have significant biological implications, since insulin fibrillation is known to cause injection amyloidosis and our data may help in designing lead drug molecules and development of potential therapeutic strategies.
 
Publisher NATURE PUBLISHING GROUP
 
Date 2016-01-15T06:40:52Z
2016-01-15T06:40:52Z
2015
 
Type Article
 
Identifier SCIENTIFIC REPORTS, 5
2045-2322
http://dx.doi.org/10.1038/srep17599
http://dspace.library.iitb.ac.in/jspui/handle/100/17957
 
Language en