title: Membrane disordering is not sufficient for membrane permeabilization by islet amyloid polypeptide: studies of IAPP(20-29) fragments.
abstract: A key factor in the development of type II diabetes is the loss of insulin-producing beta-cells. Human islet amyloid polypeptide protein (human-IAPP) is believed to play a crucial role in this process by forming small aggregates that exhibit toxicity by disrupting the cell membrane. The actual mechanism of membrane disruption is complex and appears to involve an early component before fiber formation and a later component associated with fiber formation on the membrane. By comparing the peptide-lipid interactions derived from solid-state NMR experiments of two IAPP fragments that cause membrane disordering to IAPP derived peptides known to cause significant early membrane permeabilization, we show here that membrane disordering is not likely to be sufficient by itself to cause the early membrane permeabilization observed by IAPP, and may play a lesser role in IAPP membrane disruption than expected.
authors.affiliation: Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Brender
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Heyl
authors.forename: Shyamprasad
authors.initials: S
authors.lastname: Samisetti
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Kotler
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Osborne
authors.forename: Ranadheer R
authors.initials: RR
authors.lastname: Pesaru
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002463:Cell Membrane Permeability; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D053835:Unilamellar Liposomes