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Defective glucose-stimulated insulin release in the diabetic Goto-Kakizaki (GK) rat coincides with reduced activity of the islet carbon monoxide signaling pathway

Mosén, Henrik LU ; Salehi, Albert ; Alm, Per LU ; Henningsson, Ragnar LU ; Jimenez, Javier LU ; Ostenson, C G ; Efendic, S and Lundquist, Ingmar LU (2005) In Endocrinology 146(3). p.1553-1558
Abstract
The Goto-Kakizaki (GK) rat displays a markedly reduced insulin response to glucose, a defect that is thought to be coupled to an impaired glucose signaling in the beta-cell. We have examined whether carbon monoxide (CO), derived from beta-cell heme oxygenase (HO), might be involved in the secretory dysfunction. Immunocytochemical labeling of constitutive HO (HO-2) showed no overt difference in fluorescence pattern in islets from GK vs. Wistar controls. However, isolated islets from GK rats displayed a markedly impaired HO activity measured as CO production (-50%), and immunoblotting revealed an approximately 50% reduction of HO-2 protein expression compared with Wistar controls. Furthermore, there was a prominent expression of inducible HO... (More)
The Goto-Kakizaki (GK) rat displays a markedly reduced insulin response to glucose, a defect that is thought to be coupled to an impaired glucose signaling in the beta-cell. We have examined whether carbon monoxide (CO), derived from beta-cell heme oxygenase (HO), might be involved in the secretory dysfunction. Immunocytochemical labeling of constitutive HO (HO-2) showed no overt difference in fluorescence pattern in islets from GK vs. Wistar controls. However, isolated islets from GK rats displayed a markedly impaired HO activity measured as CO production (-50%), and immunoblotting revealed an approximately 50% reduction of HO-2 protein expression compared with Wistar controls. Furthermore, there was a prominent expression of inducible HO (HO-1) in GK islets. Incubation of isolated islets showed that the glucose-stimulated CO production and the glucose-stimulated insulin response were considerably reduced in GK islets compared with Wistar islets. Addition of the HO activator hemin or gaseous CO to the incubation media brought about a similar amplification of glucose-stimulated insulin release in GK and Wistar islets, suggesting that distal steps in the HO-CO signaling pathway were not appreciably affected. We conclude that the defective insulin response to glucose in the GK rat can be explained, at least in part, by a marked impairment of the glucose-HO-CO signaling pathway as manifested by a prominent decrease in glucose stimulation of islet CO production and a reduced expression of HO-2. A possible role of HO-1 expression as a compensatory mechanism in the GK islets is presently unclear. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrinology
volume
146
issue
3
pages
1553 - 1558
publisher
Oxford University Press
external identifiers
  • pmid:15564331
  • wos:000227035400067
  • scopus:14244268391
ISSN
0013-7227
DOI
10.1210/en.2004-0851
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Clinical Physiology (Lund) (013013000), Islet cell physiology (013212142), Pathology, (Lund) (013030000), Department of Experimental Medical Science (013210000)
id
21ee1192-7452-4610-8d8d-df5f0b6cb4fe (old id 253772)
date added to LUP
2016-04-01 11:45:49
date last changed
2022-01-26 17:51:11
@article{21ee1192-7452-4610-8d8d-df5f0b6cb4fe,
  abstract     = {{The Goto-Kakizaki (GK) rat displays a markedly reduced insulin response to glucose, a defect that is thought to be coupled to an impaired glucose signaling in the beta-cell. We have examined whether carbon monoxide (CO), derived from beta-cell heme oxygenase (HO), might be involved in the secretory dysfunction. Immunocytochemical labeling of constitutive HO (HO-2) showed no overt difference in fluorescence pattern in islets from GK vs. Wistar controls. However, isolated islets from GK rats displayed a markedly impaired HO activity measured as CO production (-50%), and immunoblotting revealed an approximately 50% reduction of HO-2 protein expression compared with Wistar controls. Furthermore, there was a prominent expression of inducible HO (HO-1) in GK islets. Incubation of isolated islets showed that the glucose-stimulated CO production and the glucose-stimulated insulin response were considerably reduced in GK islets compared with Wistar islets. Addition of the HO activator hemin or gaseous CO to the incubation media brought about a similar amplification of glucose-stimulated insulin release in GK and Wistar islets, suggesting that distal steps in the HO-CO signaling pathway were not appreciably affected. We conclude that the defective insulin response to glucose in the GK rat can be explained, at least in part, by a marked impairment of the glucose-HO-CO signaling pathway as manifested by a prominent decrease in glucose stimulation of islet CO production and a reduced expression of HO-2. A possible role of HO-1 expression as a compensatory mechanism in the GK islets is presently unclear.}},
  author       = {{Mosén, Henrik and Salehi, Albert and Alm, Per and Henningsson, Ragnar and Jimenez, Javier and Ostenson, C G and Efendic, S and Lundquist, Ingmar}},
  issn         = {{0013-7227}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{1553--1558}},
  publisher    = {{Oxford University Press}},
  series       = {{Endocrinology}},
  title        = {{Defective glucose-stimulated insulin release in the diabetic Goto-Kakizaki (GK) rat coincides with reduced activity of the islet carbon monoxide signaling pathway}},
  url          = {{http://dx.doi.org/10.1210/en.2004-0851}},
  doi          = {{10.1210/en.2004-0851}},
  volume       = {{146}},
  year         = {{2005}},
}