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The mechanism of insulin action on i...

Hall, Jennifer Larson.

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The mechanism of insulin action on islet amyloid polypeptide fiber formation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The mechanism of insulin action on islet amyloid polypeptide fiber formation./
Author:	Hall, Jennifer Larson.
Description:	113 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4819.
Contained By:	Dissertation Abstracts International64-10B.
Subject:	Biophysics, General. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3109403
ISBN:	0496569457

The mechanism of insulin action on islet amyloid polypeptide fiber formation.
Hall, Jennifer Larson.

The mechanism of insulin action on islet amyloid polypeptide fiber formation. - 113 p.

Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4819.

Thesis (Ph.D.)--Yale University, 2003.

The pathology of type II diabetes includes the presence of cytotoxic amyloid deposits in the islets of Langerhans, The main component of these deposits, islet amyloid polypeptide (IAPP), is a hormone involved in glucose metabolism and is normally co-secreted with insulin by the beta-cells of the pancreas. Although the role of islet amyloid in the pathogenesis of the disease is unclear, amyloid is localized in vivo with areas of cell degeneration and amyloid fibers produced in vitro are toxic to cultured cells.

ISBN: 0496569457Subjects--Topical Terms:

1019105
Biophysics, General.

The mechanism of insulin action on islet amyloid polypeptide fiber formation.
LDR:03273nmm 2200301 4500 001 1844070
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020 $a 0496569457
035 $a (UnM)AAI3109403
035 $a AAI3109403
040 $a UnM $c UnM
100 1 $a Hall, Jennifer Larson. $3 1932274
245 1 4 $a The mechanism of insulin action on islet amyloid polypeptide fiber formation.
300 $a 113 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4819.
500 $a Director: Andrew Miranker.
502 $a Thesis (Ph.D.)--Yale University, 2003.
520 $a The pathology of type II diabetes includes the presence of cytotoxic amyloid deposits in the islets of Langerhans, The main component of these deposits, islet amyloid polypeptide (IAPP), is a hormone involved in glucose metabolism and is normally co-secreted with insulin by the beta-cells of the pancreas. Although the role of islet amyloid in the pathogenesis of the disease is unclear, amyloid is localized in vivo with areas of cell degeneration and amyloid fibers produced in vitro are toxic to cultured cells.
520 $a The mechanism by which soluble IAPP converts into insoluble aggregates has not been well established. In order to better understand this process, a novel method for monitoring fibrillogenesis has been developed. The approach, based on electrospray ionization mass spectrometry, is complementary to existing assays of fiber formation as it monitors directly the consumption of soluble IAPP rather than the formation of end product. We use this method to monitor the consumption of soluble IAPP in seeded reactions as well as measure the equilibrium monomer concentration after the reaction is complete.
520 $a Changes in the concentration of IAPP relative to other granule components may be responsible for amyloid formation in type II diabetes. To investigate the mechanism by which insulin acts on fiber formation, we perform in vitro IAPP fibrillogenesis experiments in the presence and absence of insulin. We find that insulin is an exceptionally potent inhibitor. IAPP fiber formation in vitro requires a minimum of three steps: fiber-independent nucleation, elongation, and fiber-dependent nucleation. Furthermore, these steps are attenuated by the presence of a dispersed-phase transition. We interpret this data in the context of the phase-mediated fibrillogenesis model (PMF) and conclude through experiment and kinetic simulation that the dominant effect of insulin is to act on the elongation portion of the reaction. Unusually, the magnitude of the inhibitory effect is dependent on insulin concentration, yet independent of IAPP concentration. This indicates that a disruption in insulin:IAPP ratios is unlikely to be the primary cause of amyloid formation. These results further suggest that amyloid formation in type II diabetes involves either an additional agent that acts as an accelerant, or a step that segregates IAPP from insulin.
590 $a School code: 0265.
650 4 $a Biophysics, General. $3 1019105
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0786
690 $a 0487
710 2 0 $a Yale University. $3 515640
773 0 $t Dissertation Abstracts International $g 64-10B.
790 1 0 $a Miranker, Andrew, $e advisor
790 $a 0265
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3109403