Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic beta-cells
Lundquist, Ingmar LU ; Alm, Per LU ; Salehi, S Albert LU
; Henningsson, Ragnar
LU
; Grapengiesser, E
and Hellman, B
(2003)
In American Journal of Physiology: Endocrinology and Metabolism
285(5).
p.1055-1063
- Abstract
- A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](i)) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+](i). Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold... (More)
- A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](i)) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+](i). Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold higher generation of CO ( 1 nmol.min(-1).mg protein(-1)) than the lean controls. This is 100-fold the rate for their constitutive production of NO. Moreover, islets from ob/ob mice showed a threefold increase in HO-2 expression and expressed inducible HO (HO-1). The presence of an excessive islet production of CO in the ob/ob mouse had its counterpart in a pronounced suppression of the glucose-stimulated insulin release from islets exposed to the HO inhibitor Zn-protoporhyrin (10 muM) and in a 16 times higher frequency of [Ca2+](i) transients in their beta-cells. Hemin (0.1 and 1.0 muM), the natural substrate for HO, promoted the appearance of [Ca2+](i) transients, and 10 muM of the HO inhibitors Zn-protoporphyrin and Cr-mesoporphyrin had a suppressive action both on the firing of transients and their synchronization. It is concluded that the increased islet production of CO contributes to the hyperinsulinemia in ob/ob mice. In addition to serving as a positive modulator of glucose-stimulated insulin release, CO acts as a messenger propagating Ca2+ signals with coordinating effects on the beta-cell rhythmicity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/299513
- author
- Lundquist, Ingmar
LU
; Alm, Per
LU
; Salehi, S Albert
LU
; Henningsson, Ragnar
LU
; Grapengiesser, E
and Hellman, B
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- calcium ion, carbon monoxide
- in
- American Journal of Physiology: Endocrinology and Metabolism
- volume
- 285
- issue
- 5
- pages
- 1055 - 1063
- publisher
- American Physiological Society
- external identifiers
-
- pmid:14534076
- wos:000185822500015
- scopus:0142052859
- ISSN
- 1522-1555
- DOI
- 10.1152/ajpendo.00498.2002
- language
- English
- LU publication?
- yes
- id
- e3bf891d-dc2e-420a-8203-bc00748a0341 (old id 299513)
- date added to LUP
- 2016-04-01 16:10:10
- date last changed
- 2022-03-14 22:36:05
@article{e3bf891d-dc2e-420a-8203-bc00748a0341,
abstract = {{A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](i)) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+](i). Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold higher generation of CO ( 1 nmol.min(-1).mg protein(-1)) than the lean controls. This is 100-fold the rate for their constitutive production of NO. Moreover, islets from ob/ob mice showed a threefold increase in HO-2 expression and expressed inducible HO (HO-1). The presence of an excessive islet production of CO in the ob/ob mouse had its counterpart in a pronounced suppression of the glucose-stimulated insulin release from islets exposed to the HO inhibitor Zn-protoporhyrin (10 muM) and in a 16 times higher frequency of [Ca2+](i) transients in their beta-cells. Hemin (0.1 and 1.0 muM), the natural substrate for HO, promoted the appearance of [Ca2+](i) transients, and 10 muM of the HO inhibitors Zn-protoporphyrin and Cr-mesoporphyrin had a suppressive action both on the firing of transients and their synchronization. It is concluded that the increased islet production of CO contributes to the hyperinsulinemia in ob/ob mice. In addition to serving as a positive modulator of glucose-stimulated insulin release, CO acts as a messenger propagating Ca2+ signals with coordinating effects on the beta-cell rhythmicity.}},
author = {{Lundquist, Ingmar and Alm, Per and Salehi, S Albert and Henningsson, Ragnar and Grapengiesser, E and Hellman, B}},
issn = {{1522-1555}},
keywords = {{calcium ion; carbon monoxide}},
language = {{eng}},
number = {{5}},
pages = {{1055--1063}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology: Endocrinology and Metabolism}},
title = {{Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic beta-cells}},
url = {{http://dx.doi.org/10.1152/ajpendo.00498.2002}},
doi = {{10.1152/ajpendo.00498.2002}},
volume = {{285}},
year = {{2003}},
}