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Postnatally disturbed pancreatic islet cell distribution in human islet amyloid polypeptide transgenic mice

Wong, HY; Ahrén, Bo LU ; Lips, CJM; Hoppener, JWM and Sundler, Frank LU (2003) In Regulatory Peptides 113(1-3). p.89-94
Abstract
Objective: Islet amyloid polypeptide (IAPP)/amylin is produced by the pancreatic islet beta-cells, which also produce insulin. To study potential functions of IAPP, we have generated transgenic mice overexpressing human IAPP (hIAPP) in the beta-cells. These mice show a diabetic phenotype when challenged with an oral glucose load. In this study, we examined the islet cytoarchitecture in the hIAPP mice by examining islet cell distribution in the neonatal period, as well as 1, 3 and 6 months after birth. Results: Neonatal transgenic mice exhibited normal islet cell distribution with beta-cells constituting the central islet portion, whereas glucagon and somatostatin-producing cells constituted the peripheral zone. In contrast, in hIAPP... (More)
Objective: Islet amyloid polypeptide (IAPP)/amylin is produced by the pancreatic islet beta-cells, which also produce insulin. To study potential functions of IAPP, we have generated transgenic mice overexpressing human IAPP (hIAPP) in the beta-cells. These mice show a diabetic phenotype when challenged with an oral glucose load. In this study, we examined the islet cytoarchitecture in the hIAPP mice by examining islet cell distribution in the neonatal period, as well as 1, 3 and 6 months after birth. Results: Neonatal transgenic mice exhibited normal islet cell distribution with beta-cells constituting the central islet portion, whereas glucagon and somatostatin-producing cells constituted the peripheral zone. In contrast, in hIAPP transgenic mice at the age of 1 month, the glucagon-immunoreactive (IR) cells were dispersed throughout the islets. Furthermore, at the age of 3 and 6 months, the islet organisation was similarly severely disturbed as at 1 month. Expression of both endogenous mouse IAPP and transgenic hIAPP was clearly higher in 6-month-old mice as compared to newborns, as revealed by mRNA in situ hybridisation. Conclusions: Mice transgenic for hIAPP have islets with disrupted islet cytoarchitecture in the postnatal period, particularly affecting the distribution of glucagon-IR cells. This islet cellular phenotype of hIAPP transgenic mice is similar to that of other mouse models of experimental diabetes and might contribute to the impaired glucose homeostasis. (C) 2003 Elsevier Science B.V All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
islet development, alpha-cell distribution, glucagon, islet amyloid polypeptide, islets of Langerhans, amylin
in
Regulatory Peptides
volume
113
issue
1-3
pages
89 - 94
publisher
Elsevier
external identifiers
  • wos:000182628300012
  • pmid:12686466
  • scopus:12444263414
ISSN
1873-1686
DOI
language
English
LU publication?
yes
id
2caada93-b451-4a95-8f9e-44a0d4ecfbef (old id 312411)
date added to LUP
2007-09-24 09:38:46
date last changed
2018-05-29 10:15:01
@article{2caada93-b451-4a95-8f9e-44a0d4ecfbef,
  abstract     = {Objective: Islet amyloid polypeptide (IAPP)/amylin is produced by the pancreatic islet beta-cells, which also produce insulin. To study potential functions of IAPP, we have generated transgenic mice overexpressing human IAPP (hIAPP) in the beta-cells. These mice show a diabetic phenotype when challenged with an oral glucose load. In this study, we examined the islet cytoarchitecture in the hIAPP mice by examining islet cell distribution in the neonatal period, as well as 1, 3 and 6 months after birth. Results: Neonatal transgenic mice exhibited normal islet cell distribution with beta-cells constituting the central islet portion, whereas glucagon and somatostatin-producing cells constituted the peripheral zone. In contrast, in hIAPP transgenic mice at the age of 1 month, the glucagon-immunoreactive (IR) cells were dispersed throughout the islets. Furthermore, at the age of 3 and 6 months, the islet organisation was similarly severely disturbed as at 1 month. Expression of both endogenous mouse IAPP and transgenic hIAPP was clearly higher in 6-month-old mice as compared to newborns, as revealed by mRNA in situ hybridisation. Conclusions: Mice transgenic for hIAPP have islets with disrupted islet cytoarchitecture in the postnatal period, particularly affecting the distribution of glucagon-IR cells. This islet cellular phenotype of hIAPP transgenic mice is similar to that of other mouse models of experimental diabetes and might contribute to the impaired glucose homeostasis. (C) 2003 Elsevier Science B.V All rights reserved.},
  author       = {Wong, HY and Ahrén, Bo and Lips, CJM and Hoppener, JWM and Sundler, Frank},
  issn         = {1873-1686},
  keyword      = {islet development,alpha-cell distribution,glucagon,islet amyloid polypeptide,islets of Langerhans,amylin},
  language     = {eng},
  number       = {1-3},
  pages        = {89--94},
  publisher    = {Elsevier},
  series       = {Regulatory Peptides},
  title        = {Postnatally disturbed pancreatic islet cell distribution in human islet amyloid polypeptide transgenic mice},
  url          = {http://dx.doi.org/},
  volume       = {113},
  year         = {2003},
}