Isolation and characterization of novel intestinal polypeptides of the enteroinsular and brain-gut axes and of macrophages
Author: Chen, Zheng-wang
Date: 1997-12-12
Location: Farmakologens föreläsningssal
Time: 10.00
Abstract
The gastrointestinal tract has been recognized as our largest endocrine
organ, fromwhich many peptide hormones, neuropep- tides and growth
factors have been isolated.There is also increasing evidence that the
gastrointestinal tract can be consideredas our largest immune organ, from
which many antibacterial peptides, cy tokines,cytotoxins and chemokines
have been characterized.
Different entero-endocrine cells, peptidergic nerve terminals and immune
cells arefound in this organ.
This thesis describes the isolation and characterization, from intestinal
tissues,of seven polypeptides, five porcine [daintain/AIF1, diazepam
binding inhibitor (DBI),dopuin, pancreatic polypeptide (PP), vimentin-37]
and two from chicken (DBI1-86 andDBI35-86). These peptides were first
detected in chromatographic peptide fractionsthat influenced the
glucose-induced secretion of insulin from rat, isolated pancreaticglands
or islets. Purification was guided by monitoring this effect or
chemicallyby analysis for the presence of cyst(e)ine peptides.
The polypeptides dopuin (do, many; pu, proline) and daintain- /AIF1 (da,
big; in,influencing; tai, peptide; in, insulin secretion /allograft
inflammatory factor 1)represent novel structures. The multifunctional
peptide DBI and the peptide hormonePP have now been isolated from
intestinal tissues, while chicken DBI and its novel,processed form
DBI35-86 represent peptides now isolated from avian sources. Bothof the
purified chicken DBI forms inhibit glucose-induced insulin release in
vitro,and were not known in structure earlier.
Dopuin is a 62-residue polypeptide with a high content of pro-line in its
N-terminalpart and a high proportion of histidine in its C-terminal part.
Both proline andhistidine are important residues for specific structures
and specialized functions.Six half-cystine resi-dues are present and
shown to be involved in three intrachaindi-sulphide bridges (Cys22-25,
23-54, 35-44) which contribute to a tightly foldedcore segment in the
molecular structure. At 10 nM concentration, the peptide hasan inhibitory
tendency on glucose induced insulin release in vitro.
Daintain/AIFI consists of 146 amino acid residues and is N-ter- minally
acetyl blocked.An internal 44-residue segment with a sequence pattern
(---KR--- KK---GKR---) resemblesthat found in the structural theme of
peptide hormone precursors and of the GKR segmentfor C-terminal amide
formation during the processing of peptide hormones. Daintain/AIFIis
immunohistochemically localized to microglial cells in the central
nervous system,to macrophages, and to tissue-specialized macrophages such
as dendritic or Kupffer'scells in the immune system of different tissues.
Its weakly insulin-suppressing activityin vitro, dual influence on
glucose-stimulated insulin secretion in vivo and relativeabundance in
macrophages of the pancreatic islets of prediabetic and newly diabeticBB
rats raise the possibility that daintain/AIFI has a role in the
pathogenesis ofinsulin dependent diabetes mellitus and other autoimmune
diseases.
Issue date: 1997-11-21
Publication year: 1997
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