Defective glucose-stimulated insulin release in the diabetic Goto-Kakizaki (GK) rat coincides with reduced activity of the islet carbon monoxide signaling pathway
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/253772
- author
- Mosén, Henrik LU ; Salehi, Albert ; Alm, Per LU ; Henningsson, Ragnar LU ; Jimenez, Javier LU ; Ostenson, C G ; Efendic, S and Lundquist, Ingmar LU
- organization
- publishing date
- 2005
- 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}}, }