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Osteopontin affects insulin vesicle localization and Ca2+ homeostasis in pancreatic beta cells from female mice

Wendt, Anna LU ; Mollet, Ines LU ; Knutsson, Anki LU ; Bolmgren, Victor S.; Hultgårdh, Anna LU ; Gomez, Maria F. LU and Eliasson, Lena LU (2017) In PLoS ONE 12(1).
Abstract

Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT. Analysis of the insulin granule distribution in the beta cells showed that although OPN-/- and WT beta cells have the same number of insulin granules... (More)

Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT. Analysis of the insulin granule distribution in the beta cells showed that although OPN-/- and WT beta cells have the same number of insulin granules OPN-/- beta cells have significantly fewer docked granules. Both OPN-/- and WT islets displayed synchronized Ca2+ oscillations indicative of an intact beta cell communication. OPN-/- islets displayed higher intracellular Ca2+ concentrations when stimulated with 16.7 mM glucose than WT islets and the initial dip upon elevated glucose concentrations (which is associated with Ca2+ uptake into ER) was significantly lower in these islets. Glucose-induced insulin secretion was similar in OPN-/- and WT islets. Likewise, non-fasted blood glucose levels were the same in both groups. In summary, deletion of OPN results in several minor beta-cell defects that can be compensated for in a healthy system.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Type 2 diabetesmellitus, Osteopontin, mice, Ca homeostasis
in
PLoS ONE
volume
12
issue
1
publisher
Public Library of Science
external identifiers
  • scopus:85010295281
  • pmid:28107503
  • wos:000392405300148
ISSN
1932-6203
DOI
10.1371/journal.pone.0170498
language
English
LU publication?
yes
id
dee4db88-5c3a-44b1-9da5-fde6aef1f488
date added to LUP
2017-02-16 11:43:25
date last changed
2018-01-07 11:50:18
@article{dee4db88-5c3a-44b1-9da5-fde6aef1f488,
  abstract     = {<p>Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN<sup>-/-</sup>). Ultra-structural analyzes of islets from OPN<sup>-/-</sup> and WT mice indicated weaker cell-cell connections between the islet cells in the OPN<sup>-/-</sup> mouse compared to WT. Analysis of the insulin granule distribution in the beta cells showed that although OPN<sup>-/-</sup> and WT beta cells have the same number of insulin granules OPN<sup>-/-</sup> beta cells have significantly fewer docked granules. Both OPN<sup>-/-</sup> and WT islets displayed synchronized Ca<sup>2+</sup> oscillations indicative of an intact beta cell communication. OPN<sup>-/-</sup> islets displayed higher intracellular Ca<sup>2+</sup> concentrations when stimulated with 16.7 mM glucose than WT islets and the initial dip upon elevated glucose concentrations (which is associated with Ca<sup>2+</sup> uptake into ER) was significantly lower in these islets. Glucose-induced insulin secretion was similar in OPN<sup>-/-</sup> and WT islets. Likewise, non-fasted blood glucose levels were the same in both groups. In summary, deletion of OPN results in several minor beta-cell defects that can be compensated for in a healthy system.</p>},
  articleno    = {e0170498},
  author       = {Wendt, Anna and Mollet, Ines and Knutsson, Anki and Bolmgren, Victor S. and Hultgårdh, Anna and Gomez, Maria F. and Eliasson, Lena},
  issn         = {1932-6203},
  keyword      = {Type 2 diabetesmellitus,Osteopontin,mice,Ca homeostasis},
  language     = {eng},
  month        = {01},
  number       = {1},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Osteopontin affects insulin vesicle localization and Ca<sup>2+</sup> homeostasis in pancreatic beta cells from female mice},
  url          = {http://dx.doi.org/10.1371/journal.pone.0170498},
  volume       = {12},
  year         = {2017},
}