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beta-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia

Egerod, Kristoffer L.; Jin, Chunyu; Petersen, Pia Steen; Wierup, Nils LU ; Sundler, Frank LU ; Holst, Birgitte and Schwartz, Thue W. (2011) In International Journal of Endocrinology
Abstract
Mice deficient in the zinc-sensor GPR39, which has been demonstrated to protect cells against endoplasmatic stress and cell death in vitro, display moderate glucose intolerance and impaired glucose-induced insulin secretion. Here, we use the Tet-On system under the control of the proinsulin promoter to selectively overexpress GPR39 in the beta cells in a double transgenic mouse strain and challenge them with multiple low doses of streptozotocin, which in the wild-type littermates leads to a gradual increase in nonfasting glucose levels and glucose intolerance observed during both food intake and OGTT. Although the overexpression of the constitutively active GPR39 receptor in animals not treated with streptozotocin appeared by itself to... (More)
Mice deficient in the zinc-sensor GPR39, which has been demonstrated to protect cells against endoplasmatic stress and cell death in vitro, display moderate glucose intolerance and impaired glucose-induced insulin secretion. Here, we use the Tet-On system under the control of the proinsulin promoter to selectively overexpress GPR39 in the beta cells in a double transgenic mouse strain and challenge them with multiple low doses of streptozotocin, which in the wild-type littermates leads to a gradual increase in nonfasting glucose levels and glucose intolerance observed during both food intake and OGTT. Although the overexpression of the constitutively active GPR39 receptor in animals not treated with streptozotocin appeared by itself to impair the glucose tolerance slightly and to decrease the beta-cell mass, it nevertheless totally protected against the gradual hyperglycemia in the steptozotocin-treated animals. It is concluded that GPR39 functions in a beta-cell protective manner and it is suggested that it is involved in some of the beneficial, beta-cell protective effects observed for Zn(++) and that GPR39 may be a target for antidiabetic drug intervention. (Less)
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organization
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type
Contribution to journal
publication status
published
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in
International Journal of Endocrinology
publisher
Hindawi Publishing Corporation
external identifiers
  • wos:000298676300001
  • scopus:84855608764
ISSN
1687-8337
DOI
10.1155/2011/401258
language
English
LU publication?
yes
id
0ac50ca1-9423-43bb-ad66-e5414fd6b75a (old id 2494401)
date added to LUP
2012-05-07 14:47:10
date last changed
2017-03-26 03:12:15
@article{0ac50ca1-9423-43bb-ad66-e5414fd6b75a,
  abstract     = {Mice deficient in the zinc-sensor GPR39, which has been demonstrated to protect cells against endoplasmatic stress and cell death in vitro, display moderate glucose intolerance and impaired glucose-induced insulin secretion. Here, we use the Tet-On system under the control of the proinsulin promoter to selectively overexpress GPR39 in the beta cells in a double transgenic mouse strain and challenge them with multiple low doses of streptozotocin, which in the wild-type littermates leads to a gradual increase in nonfasting glucose levels and glucose intolerance observed during both food intake and OGTT. Although the overexpression of the constitutively active GPR39 receptor in animals not treated with streptozotocin appeared by itself to impair the glucose tolerance slightly and to decrease the beta-cell mass, it nevertheless totally protected against the gradual hyperglycemia in the steptozotocin-treated animals. It is concluded that GPR39 functions in a beta-cell protective manner and it is suggested that it is involved in some of the beneficial, beta-cell protective effects observed for Zn(++) and that GPR39 may be a target for antidiabetic drug intervention.},
  articleno    = {401258},
  author       = {Egerod, Kristoffer L. and Jin, Chunyu and Petersen, Pia Steen and Wierup, Nils and Sundler, Frank and Holst, Birgitte and Schwartz, Thue W.},
  issn         = {1687-8337},
  language     = {eng},
  publisher    = {Hindawi Publishing Corporation},
  series       = {International Journal of Endocrinology},
  title        = {beta-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia},
  url          = {http://dx.doi.org/10.1155/2011/401258},
  year         = {2011},
}