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2015 ; 5
(ä): 17599
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Inhibition of insulin fibrillation by osmolytes: Mechanistic insights
#MMPMID26616401
Choudhary S
; Kishore N
; Hosur RV
Sci Rep
2015[Nov]; 5
(ä): 17599
PMID26616401
show ga
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.